Automated electrophoresis gel manipulation apparatus and method

ABSTRACT

An automated, computer controlled assembly is provided for continuously processing a large number of electrophoresis gels. The assembly includes a loading assembly for loading a gel onto a carrier, a gel staining assembly and a scanning and cutting assembly. The staining assembly and the scanning and cutting assembly each include a robotic arm that is able to capture a gel and transfer the gel to selected work stations and can transfer the gel between the respective robotic arms.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. § 119(e) ofProvisional Application No. 60/281,000, filed Apr. 4, 2001, for“Automated Electrophoresis Gel Staining, Imaging and Cutting Apparatusand Method”, which is hereby incorporated by reference in its entirety.This application is also a continuation-in-part application of U.S.application Ser. No. 09/783,132, filed Feb. 15, 2001, for “GelManipulation Apparatus”, which is a continuation-in-part application ofSer. No. 09/504,494, filed Feb. 15, 2000, for “Electrophoresis Gel Clampfor Handling and Transport”, and Ser. No. 09/504,493, filed Feb. 15,2000, for “Slab Gel Processing Tank”. This application is acontinuation-in-part application of Ser. No. 09/978,574, filed Oct. 18,2001, for “Method and Apparatus for Relieving Stress in anElectrophoresis Gel Slab” and Ser. No. 09/859,664, filed May 18, 2001,for “Automated Apparatus for Separating a Biological Sample from aTwo-Dimensional Electrophoresis Gel”, which applications are herebyincorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention is directed to a method and apparatus formanipulating an electrophoresis gel. The invention is also directed toan automated, computer controlled robotic assembly for transferring anelectrophoresis gel between various work stations for treating the gels.

BACKGROUND OF THE INVENTION

Isoelectric focusing (IEF) is an electrophoretic technique that iscommonly used for the analysis, separation and purification of variousbiological materials, and particularly proteins. Since many of thecomplex molecules of biological interest are amphoteric in nature, theyare typically amenable to IEF separation. Gel electrophoresis is aprocess that is commonly used for protein and DNA analysis.

The separation of macromolecules, and particularly proteins, often iscarried out by two-dimensional electrophoresis separation. Thetwo-dimensional electrophoresis separation typically involves thesequential separation by isoelectric focusing of a sample in a gel tubefollowed by slab gel electrophoresis. The isoelectric focusing processin the gel tube is often referred to as first dimension separation.

In the first dimension separation, an isoelectric focusing gel, such asacrylamide, is placed or polymerized in a tube. The open ends of thetube are positioned in a tank with a buffer solution at each end of thetube. One end of the tube is positioned in a bath of a buffer solutionsuch as sodium hydroxide solution. The other end of the tube ispositioned in a bath of a second buffer solution such as a phosphoricacid solution. An electric current is applied to the two buffersolutions. The current together with ampholytes incorporated into thegel composition or titratable gel monomers incorporated into the gel,provides a pH gradient through the gel along the length of the tube. Thesample to be analyzed is applied to a one end of the gel in the tube andan electric current is applied to an electrode in each of the buffersolutions. The molecules in the sample migrate through the gel under theinfluence of the electric potential until they reach their respectiveisoelectric point.

Slab gel electrophoresis, often referred to as second dimensionseparation, utilizes an electrophoresis gel molded between two glassplates. A gel strip or cylinder in which the protein sample has beenresolved by the first dimension isoelectric focusing is placed along oneedge of the slab gel. The ends of the gel slab are positioned in abuffer solution and an electric current is applied to each end of thegel. The proteins are then allowed to migrate through the gel slab underan applied voltage.

Charged detergents, such as sodium dodecyl sulfate, contained in theslab gel bind to the protein molecules. The detergents tend to unfoldthe protein molecules into rods having a length proportional to thelength of the polypeptide chain and thus proportional to the molecularweight of the polypeptide. A protein complexed with a charged detergentis highly charged, which causes the protein-detergent complex to move inan applied electric field. When the slab gel, such as a polyacrylamidegel, functions as a sieve, the movement of the longer and highermolecular weight molecules is retarded compared to the shorter, lowermolecular weight molecules.

Electrophoresis separation is generally labor intensive since numeroussamples are run simultaneously. Generally, the gel tubes are preparedand placed in a suitable tank of buffer solutions. The protein samplesare then manually placed on the end of a gel tube. When hundreds ofprotein samples are prepared daily for isoelectric focusing, the manualsteps significantly increase the time requirements for performing thefirst dimension separation.

The resolution of the separation methods are sufficient to separate atleast 150 proteins from a mixture. The first dimension isoelectricfocusing separation followed by the second dimension SDS electrophoresisseparation can result in the resolution of as many as 22,000 proteinsfrom a single sample. A critical step in obtaining high resolutiontwo-dimensional electrophoresis is to coordinate the first dimensionseparation with the second dimension separation.

The gel slab is removed from the glass plates and immersed in a seriesof baths containing various staining agents. Typically, the gel slabsare manually transferred from a stain bath to various fixing solutionsand rinsing solutions. After the second dimension electrophoresisseparation, the gel is developed to stain the proteins which appear as aspot on the gel. Thereafter, a gel spot can be identified, removed fromthe slab, and analyzed.

Various automated devices are known for performing various analysisprocesses of proteins and DNA. One example is disclosed in U.S. Pat. No.5,865,975 to Bishop. The disclosed system uses an automated protein andDNA gene fragments analyzing machine where electrophoresis cells arerobotically inserted into an electrophoresis housing for producingelectrophoretic migration of the protein in one dimension. The roboticassembly rotates the cells 90° to enable separation of the fragmentsvertically in a second dimension.

The gel slabs are made of a flexible gel and care must be taken toprevent damaging or tearing the gel. During handling and manipulating,the gel slab adheres to surfaces that it contacts. As the gel is pulledfrom the surface, the gel can tear or stretch. Various devices have beenproposed for handling and manipulating gel slabs. However, these deviceshave experienced only limited success. Accordingly, there is acontinuing need in the industry for improved methods and devices forhandling and processing electrophoresis gels.

SUMMARY OF THE INVENTION

The present invention is directed to a method and apparatus formanipulating an electrophoresis gel. The invention is also directed toan automated, computer controlled system having a robotic assembly fortransferring an electrophoresis gel between various work stations fortreating and processing the gels.

Accordingly a primary aspect of the invention is to provide an automatedapparatus for manipulating an electrophoresis gel and transferring thegel from a storage tank to one or more gel processing tanks according toa preselected processing protocol for the gel.

Another aspect of the invention is to provide an automated apparatushaving a robotic arm that is controlled by a computer to selectivelytransfer an electrophoresis gel between selected work stations and tomonitor the location of the gel within the apparatus.

A further aspect of the invention is to provide a computer-controlledrobotic apparatus for manipulating an electrophoresis gel along threecoordinates so that the gel can be moved in three dimensions betweenselected work stations.

Still another aspect of the invention is to provide a computercontrolled articulated arm that is movable on a boom, where the boom canbe moved in a horizontal direction and in a vertical direction and wherethe articulated arm is movable along the length of the boom.

A further aspect of the invention is to provide an automated computercontrolled apparatus having an articulated robotic arm that is able tomove into a selected position and capture an electrophoresis gelattached to a carrier, transfer the gel to a selected location, releasethe captured gel at the selected location and substantially retrieve thegel.

Another aspect of the invention is to provide a carrier device forcapturing an electrophoresis gel where the gel can be suspended from thecarrier without damaging or tearing the gel while the gel is beingtransferred between selected locations.

Still another aspect of the invention is to provide a clamp device thatis able to capture an electrophoresis gel and suspend the gel withoutdamaging the gel.

Another aspect of the invention is to provide a clamp device having apair of jaws that are biased together by at least one magnet on each ofthe jaws.

A further aspect of the invention is to provide a staining tank for anelectrophoresis gel where the tank has an agitating assembly that isable to move the gel within the tank.

Another aspect of the invention is to provide an agitating device for anelectrophoresis gel staining tank where the agitating device moves thegel in a reciprocating motion in a substantially vertical direction.

Still another aspect of the invention is to provide a tank for treatingan electrophoresis gel where the tank has at least one wall having asurface texture that resists or inhibits the gel from adhering to thewall.

A further aspect of the invention is to provide a tank for treating anelectrophoresis gel where the tank includes at least one divider thatcan be removable to separate adjacent gels in the tank and where thedivider has a surface that inhibits the gel from adhering to thedivider.

A further aspect of the invention is to provide an automatedelectrophoresis gel processing tank having a computer controlledapparatus for identifying an electrophoresis gel and selecting aprocessing protocol specific for the gel and the biological samplecontained in the gel, transporting the gel to predetermined locationsand monitoring the location of the gel within the assembly.

The apparatus of the invention basically comprises a robotic assemblythat is controlled by a computer or central processing unit to controlthe movement of the assembly and coordinate the operation of the variousdevices of the assembly. The apparatus includes a robotic arm that isable to capture and manipulate electrophoresis gels between selectedprocessing stations in sequence and according to a selected processingprotocol for each electrophoresis gel. The computer is programmed toselectively transfer the gel to selected stations where the gel isprocessed for a predetermined period of time. At the same time thecomputer records the location of the gel and the progress of the processat each stage. The robotic assembly has an articulated arm that can bemoved to an infinite number of locations within the apparatus. In oneembodiment of the invention the robotic assembly has a boom that cantravel in a horizontal direction and in a vertical direction withrespect to the plane of the assembly. At the same time the articulatedarm can travel along the length of the boom to selected positions toenable transferring of the gel between the various locations of theapparatus.

The automated apparatus is primarily directed for use with a loadingapparatus, staining apparatus, scanning and automated cutting apparatusfor the sequential staining, scanning and cutting steps of anelectrophoresis gel staining process. The automated apparatus iscontrolled by a computer or central processing unit that is able tocontrol a robotic assembly of the staining apparatus and transfer thegel to a robotic apparatus of the scanning and cutting apparatus. Theapparatus has a plurality of staining tanks that include an agitator formoving the gel in a vertical direction to agitate the staining liquidcontinuously. The agitator includes a reciprocating frame. The gels aresuspended in the staining liquid by the frame which reciprocates in avertical direction to agitate the liquid.

The carrier of the invention is a clamp member that is able to capture agel along one edge so that the gel can be suspended vertically by theclamp without damaging the gels. The clamp has two jaws that are heldtogether by at least one magnet on each jaw. Preferably, each jaw has amagnet oriented to be attracted to the magnet on the opposing jaw toattract the clamping edges of the jaws. The magnets can be bar magnetsor a strip of magnetic material that is attached to a gripping edge ofthe jaws.

The present invention is primarily directed to an automated system forprocessing electrophoresis gel slabs to stain the protein spots thathave been separated by the electrophoresis process, identifying selectedprotein spots for protein extraction and analysis and separating theprotein spots from the gel. The automated system includes a computer foroperating the robotic assemblies and tracking the location of the gelslabs during the various phases of the process.

The apparatus of the invention basically includes a loading station forseparating the gel from the glass plates and loading the gel into acarrier for handling the gel, a gel staining station for staining theproteins in the gel, and a gel scanning and cutting station. Thecomputer controlled apparatus includes a detector for identifying a gelslab, selecting a staining protocol specific for the gel andtransferring the gel to selected staining solution in the stainingapparatus according to the selected staining protocol. The computersystems tracks the location of the gel throughout the assembly andcontrols the time and sequence of the various staining steps andcontrols the scanning and cutting steps.

The loading station receives a plurality of gel cassettes from a seconddimension electrophoresis separation process. The electrophoresis gelcassette includes an identifying marker which correlates and catalogsthe gel with a specific biological sample that was electrophoresed. Agel carrier, which is preferably a clamp, also includes an identifyingmarker. The markers are detected by the assembly to identify andassociate a carrier with the particular gel. The gel is then separatedfrom the cassette and transferred to the carrier. The carrier and theassociated gel are then placed in a holding tank of the stainingapparatus for processing at a later time.

The staining apparatus includes a computer operated robotic arm and asuitable reader for detecting the identifying marker on the gel carrier.The apparatus reads the identifying marker on the carrier to identifythe gel slab and the biological sample. The computer is connected to adatabase to identify the gel slab and the biological sample, and thenselect a staining protocol for the gel that is appropriate for theparticular biological sample. The robotic arm captures a carrier and theassociated gel and transfers the gel between selected staining, rinseand holding tanks.

At the end of the staining process, the robotic arm transfers the gel tothe gel cutting station for identifying stained gel spots in the gel andcutting the selected spots from the gel slab. The cutting stationincludes a computer controlled arm that is able to capture a tray forsupporting the gel. The tray has a flat surface for supporting the gelclamp and the gel slab during scanning and cutting steps. The roboticarm of the staining apparatus suspends the gel and moves the gel and thecarrier into contact with the tray to transfer the gel from the roboticarm to the tray. The computer controlled arm of the cutting stationtransfers the tray with the gel to a scanner. The scanner scans an imageof the gel spots and compares the image with a library of the images ofknown biological samples. Selected sample spots are identified in thegel based on a comparison of the gel with an image of a known sample.After the image of the gel is obtained, the computer operated armremoves the tray from the scanner and transfers the tray to the cuttingapparatus. The scanner is operatively connected to the cutting apparatusso that the cutting apparatus is able to cut selected spots from the geland transfer the cut gel spots to a storage vessel such as a multi-wellplate for further processing.

The computer controlled arm removes the tray from the cutting apparatusand moves the tray into position to enable the robotic arm to captureand remove the carrier and the gel from the tray. The computercontrolled arm then moves the tray to a washing station where the trayis washed and dried for subsequent use. The robotic arm transfers thespent gel to a storage vessel or to a discard station where the carrierreleases the gel into a suitable waste receptacle.

The various aspects of the invention are basically attained by providingan automated apparatus for processing an electrophoresis gel. Theapparatus comprises a first recording -assembly for receivingidentifying information of a second dimension electrophoresis gel slab.A second recording assembly receives identifying information of a gelclamp capable of supporting and transporting the gel slab. A computer iscoupled to the first recording assembly and the second recordingassembly for cataloging a selected gel slab with a selected gel clamp.

The aspects of the invention are also attained by providing an automatedapparatus for treating an electrophoresis gel slab. The apparatuscomprises a plurality of liquid treating tanks having a dimension toreceive an electrophoresis gel slab. A first robotic assembly transportselectrophoresis gels between the liquid treating tanks. A second roboticassembly manipulates a support tray having a dimension to support theelectrophoresis gel and transport the support tray between gelprocessing devices. A computer is operatively connected to the firstrobotic assembly and the second robotic assembly to coordinate movementof the first robotic arm assembly with respect to the liquid treatingtanks and the second robotic arm assembly.

The aspects of the invention are further attained by providing a gelprocessing apparatus for processing a second dimension electrophoresisgel slab. The apparatus comprises a first gel slab processing device forprocessing the gel slab. A robotic arm assembly manipulates the gel slaband maneuvers the gel slab into a processing position of the gelprocessing device. An operating computer is operatively coupled to therobotic arm for controlling the robotic arm.

The objects, advantages and salient features of the invention willbecome apparent to one skilled in the art in view of the followingdetailed description of the invention in conjunction with the annexeddrawings which form a part of this original disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

The following is a brief description of the drawings, in which:

FIG. 1 is a front view of the assembly for processing electrophoresisgels;

FIG. 2 is a perspective view of the loading station in one embodiment ofthe invention;

FIG. 3 is a front view of the loading station of FIG. 2;

FIG. 4 is an side view of the loading station of the embodiment of FIG.2;

FIG. 5 is a partial side view of the loading assembly in the embodimentof FIG. 2;

FIG. 6 is a partial cross-sectional side view of the loading assemblyshowing the bar code reader;

FIG. 6A is a side view of an alternative arrangement of the proximityswitch on the loading assembly;

FIG. 7 is a top view of the gel clamp in one embodiment of theinvention;

FIG. 8 is a side view of the gel clamp of the embodiment of FIG. 7;

FIG. 9 is a perspective view of the tray for loading a gel into a gelclamp;

FIG. 10 is a cross-sectional side view of the tray of FIG. 9 showing thegel cassette and the gel clamp;

FIG. 11 is a partial cross-sectional side view showing the tray loadingan electrophoresis gel into a gel clamp;

FIG. 12 is a perspective view of the staining assembly in one embodimentof the invention;

FIG. 13 is a front view of the robotic apparatus of the stainingassembly of the embodiment of FIG. 12;

FIG. 14 is a partial side view showing the robotic assembly;

FIG. 15 is a partial side view showing the robotic assembly placing agel clamp into a staining tank;

FIG. 16 is a partial side view showing the robotic assembly removing agel and gel clamp from a staining tank;

FIG. 17 is a partial side view showing the actuating assembly of therobotic assembly with the operating arms in the retracted position;

FIG. 18 is a side view of the robotic assembly showing the operatingarms in the extended position;

FIG. 19 is an end view showing the robotic arm in position for capturinga gel clamp;

FIG. 20 is an end view showing the robotic arm having captured a gelclamp;

FIG. 21 is a partial end view in cross-section showing the staining tankwith the textured surface to prevent the gel from adhering to thesurfaces of the gel tank;

FIG. 22 is a perspective view of the agitating assembly in oneembodiment of the invention showing the divider coupled to the wall ofthe tank;

FIG. 23 is a partial end view in cross-section of the agitating assemblyin the embodiment of FIG. 22;

FIG. 24 is a partial side view showing the agitating assembly with therail in the lowered position;

FIG. 25 is a partial side view showing the agitating assembly with therail in the raised position;

FIG. 26 is a partial cross-sectional side view showing the circulationassembly for the staining tank;

FIG. 27 is a top view of the circulation assembly of FIG. 26 for thestaining tank;

FIG. 28 is a top view of the apparatus for relieving stress in the gelwhile in a gel clamp;

FIG. 29 is a front view of the assembly for relieving stress in the gelin the embodiment of FIG. 28;

FIGS. 30A-30D show the sequential movement of the operating arms of theassembly for relieving stress in the gel;

FIG. 31 is an end view of the device for removing a gel from a gelclamp;

FIG. 32 is an end view of the device of FIG. 1 showing the gel beingreleased from the gel clamp;

FIG. 33 is a front view of the scanning and cutting assembly in oneembodiment of the invention;

FIG. 34 is a top view of the robotic arm of the assembly of FIG. 33;

FIG. 35 is a side view of the robotic arm of the assembly of FIG. 33;

FIG. 36 is a front view of robotic arm of the assembly of the embodimentof FIG. 33;

FIG. 37 is a rear view of the robotic arm showing the actuatingmechanism;

FIG. 38 is a front view of the robotic arm showing the tray supportingthe gel coupled to the robotic arm;

FIG. 39 is a top view of the tray for supporting a gel and gel clamp;

FIG. 40 is a partial cross-sectional end view showing the traysupporting a gel and gel clamp;

FIG. 41 is a side view of the robotic arm and tray in position forreceiving an electrophoresis gel;

FIG. 42 is a side view of the robotic arm with the gel partially placedon the tray;

FIG. 43 is a side view of the robotic arm after the gel and gel clamphave been transferred to the tray;

FIG. 44 is a side view showing the robotic arm pivoting the tray and gelto a horizontal position;

FIG. 45 is an end view showing the gel and gel clamp on the tray beingraised to engage a device to open the gel clamp to relieve stress in thegel;

FIG. 46 is a side view of the robotic arm in position for placing thetray and gel in a scanning device;

FIG. 47 is a side view showing the tray and gel inserted into a scanningdevice;

FIG. 48 is a side view showing the robotic arm retracted from thescanning device;

FIG. 49 is a side view of the robotic arm positioning the tray and gelinto a cutting device;

FIG. 50 is a top view the cutting device in one embodiment of theinvention;

FIG. 51 is a side view in partial cross-section of the robotic armpositioned above a washing device for washing the tray;

FIG. 52 is a side view showing the robotic arm lowering the tray intothe washing device;

FIG. 53 is a top view of the washing device showing a spray of waterdirected toward the tray;

FIG. 54 is a top view of the washing device showing a jet of air fordrying the tray;

FIG. 55 is a top view of the gel relaxer in a preferred embodiment ofthe invention;

FIG. 55A is an end view of the gel relaxer of FIG. 55:

FIG. 56 is a cross-sectional view of the gel relaxer taken along line56-56 of FIG. 55;

FIG. 57 is a side view of the gel relaxer of FIG. 55;

FIG. 58 is a partial side view of the gel relazer showing the mountingbracket for the roller in partial cross-setion;

FIG. 59 is a top view of the gel relaxer showing the tray partiallyinserted;

FIG. 60 is a top view of the gel relaxwer showing the roller displacingthe air bubbles;

FIGS. 61 and 62 are side view in cross-section showing the air bubblebeing displaced from the gel;

FIG. 63 is a top view of the gel relaxer showing the tray completelyinserted into the gel relaxer;

FIG. 64 is a partial cross-sectional end view of the gel relaxer showingthe cam member in the retracted position;

FIG. 65 is a partial cross-sectional side view of the gel relaxershowing the cam in the extended actuating position;and

FIG. 66 is a schematic diagram showing the operation of the computercontrolled assembly.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to an automated apparatus fortransferring and manipulating a work piece between various workstations. In particular, the invention is directed to a computercontrolled, automated assembly for manipulating and processing anelectrophoresis gel between various work stations.

The invention is directed to a computer operated assembly 10 forstaining, scanning and cutting samples from an electrophoresis gel slab.Typically, the gel slab is obtained from a second dimensionelectrophoresis separation process. The assembly 10 includes a computerto control the entire assembly and the handling and processing of thegel. As discussed hereinafter in greater detail, the assembly identifiesa gel, selects a processing protocol for the gel, and tracks thelocation of the gel throughout the assembly.

Referring to FIG. 1, the assembly 10 basically comprises a loadingstation including a loading assembly 12, a staining station including astaining assembly 14, and a cutting or excising station including ascanning and cutting assembly 16. The assembly 10 is a computercontrolled robotic assembly for automatically manipulating the gelsthrough the assembly with little or no manual handling of the gels. Inpreferred embodiments of the invention, the assembly 10 is able tooperate continuously to process in sequence a large number of gels, andtypically several hundred gels per day. The assembly is able to monitorcontinuously the location of a given gel throughout the assembly fromthe time the original gel slab enters the assembly to the time proteinsamples are excised from the gel and deposited in a multiwell plate. Inthis manner, a single technician can process a large number of gelswithout the need to handle each of the gels in the various processingstages. As discussed hereinafter in greater detail, assembly 10 includesa control system having a computer 13 with a display monitor (CRT) 15, akeyboard 17, and a mouse 19 or other user interface device. Thecomputer, display monitor, keyboard and mouse are hardware components toenable operator interface for programming the assembly to performselected sequences of processes, starting and stopping the process andentering process variables for performing specific functions.

Referring to FIGS. 2-11, loading assembly 12 includes a table 18 forminga work surface 20 for separating electrophoresis gels from the gelcassettes and loading the gels onto a carrier for supporting the gel andmanipulating the gels through the various process steps. Table 18includes a plurality of supporting legs 22 to support the work surfaceat a comfortable height for the technician. Work surface 20 has adimension to support a rack 24 for supporting a plurality ofelectrophoresis gel cassettes 26 and a device 28 for separating the gelfrom the cassettes 26.

Referring to FIG. 3, rack 24 includes a base 30 and a plurality ofspaced apart supports 32 extending in a substantially verticaldirection. Supports 32 are arranged to support cassettes 26 in anupright position as shown in FIG. 3. Cassettes 26 in preferredembodiments include two plates 34, typically glass, supporting anelectrophoresis gel slab 36 therebetween as shown in FIGS. 10 and 11.The electrophoresis gel slab 36 is typically a standard second dimensionelectrophoresis gel, such as an acrylamide gel, that contains proteinsor other macromolecules that have been separated by an electrophoresisseparation process as known in the art. Each cassette includes anidentifying marker 38 shown in FIG. 6 corresponding to a biologicalsample and for identifying a specific gel slab 36. The marker 38 in onepreferred embodiment is a bar code that can be read by a suitable barcode reader. In another embodiment, marker 38 can be a computer chip orother machine readable device that is able to record informationpertaining to the gel.

Referring to FIGS. 4 and 6, a detector assembly 40 is provided on worksurface 20 to detect the presence of a gel cassette 26 and to readmarker 38. In the illustrated embodiment, detector 40 includes twospaced-apart brackets 42 having a vertical slot 43 to receive a gelcassette 26 and support the cassette 26 in a vertical orientation. Aproximity switch 44 is included in at least one of the brackets 42 todetect the presence and the proper orientation of a cassette 26 inbrackets 42. A transparent window 46 is provided in work surface 20adjacent brackets 42 as shown in FIG. 6. A detector 48 capable ofdetecting and reading marker 38 is coupled to a bottom side of worksurface 20 next to window 46 and positioned in a location to enabledetector 48 to read marker 38 on cassette 26. In the illustratedembodiment, detector 48 is a bar code reader that is positioned to reada bar code marker 38 on a cassette 26. In alternative embodiments,detector 48 can be positioned on the top of work surface 20 in asuitable location to read bar code marker 38. Proximity switch 44 can belocated in other suitable locations to ensure that bar code marker 38 isproperly aligned with detector 48 so that detector 48 accurately readsmarker 38. Preferably, detector 48 is operable only when proximityswitch 44 is activated by cassette 26 that is properly aligned withdetector 48.

A support arm assembly 50 retains a plurality of gel clamps 52 thatfunction as carriers for handling an electrophoresis gel slab 36 afterit has been separated from the cassette 26. As discussed hereinafter ingreater detail, gel clamps 52 include jaws 54 and 56 as shown in FIG. 7where jaw 54 includes two apertures 58 to receive a support device. In apreferred embodiment, support arm assembly 50 includes two parallel arms60 spaced apart a distance to be received in apertures 58 of clamps 52so that clamps 52 are suspended in a stable position. Arms 60 have anouter end 62 with an upwardly extending lip 64 to prevent clamps 52 frominadvertently sliding off the end. A proximity switch 66 is includedadjacent lip 64 on a top side of at least one of arms 60 to detect thepresence of a clamp 52. In an alternative embodiment shown in FIG. 6A, aproximity switch 67 is mounted on arm 70 and is connected to a pivotallymounted arm 75.

As shown in FIG. 5, clamps 52 include an identification marker 68 suchas a bar code. Support arm assembly 50 also includes an arm 70supporting a detector or reader device such as a bar code reader 72positioned in a location to read the bar code 68 on clamp 52. In theembodiment illustrated, bar code 68 is positioned along a top end ofclamp 52 and bar code reader 72 is positioned above support arm assembly50. Proximity switch 66 is positioned on arm 60 so that the clamp 52 isaligned with bar code 68 when proximity switch 66 is actuated to enableaccurate reading of the bar code. In a preferred embodiment, proximityswitch 66 is operatively connected to detector 72 so that detector 72 isonly operable when proximity switch 66 is triggered by a gel clamp 52that is properly aligned with detector 72.

In a preferred embodiment, a flexible curtain 73 is suspended from arm70 and is aligned with the location of bar code 68 on clamp 52. Curtain73 is a flexible plastic member that bends upwardly as shown in FIG. 5when a clamp 52 is positioned against lip 64. Preferably, curtain 73 hasa length and width to enable bar code reader 72 to view and capture animage of the bar code on the gel clamp positioned against lip 64 whileblocking the view of the bar codes on the clamps behind the foremostclamp, thereby ensuring that bar code reader 72 reads only a single barcode at a time.

Detector 48, switch 44, bar code reader 68 and switch 66 are connectedto a control unit 74 such as a microprocessor to control the operationof the assembly. An actuator device 76, such as a foot operated pedal,is connected to control unit 74. In a preferred embodiment, control unit74 is operatively connected to a primary computer control system 13 forcontrolling assembly 10 as discussed hereinafter in greater detail.

In the operation of loading assembly 12, the technician selects a gelcassette 26 from rack 24 and places the cassette 26 into slots 42 ofbrackets 42. The cassette 26 is oriented with the marker 38 facing thedetector 48 as shown in FIG. 5 so that proximity switch 44 is activated.A gel clamp 52 is moved into the position on arms 60 to actuate switch66 and to be in position to enable reader 72 to read bar code 68 onclamp 52. When the cassette 26 and gel clamp 52 are in position andswitches 44 and 66 are actuated, control unit 74 produces a visual oraudio signal to the technician at which time the technician operatesactuator 76 to actuate detector 48 and bar code reader 72. Preferably,detector 48 and bar code reader 72 cannot be actuated until switches 44and 66 are actuated to ensure the accurate and simultaneous reading ofthe respective bar code on clamp 52 and cassette 26. The detector 48reads the marker 38 while reader 72 reads bar code 68 so that controlunit 74 associates a specific gel 36 with-a gel clamp 52. Control unit74 is able to transfer a signal to the operating computer to identify aparticular gel and sample with a gel clamp.

Gel clamp 52 and the associated cassette 26 are then placed in tray 78that contains a liquid, such as deionized water. The plates 34 of gelcassette 26 are separated and gel slab 36 is transferred to clamp 52.Clamp 52 and the captured gel slab 36 are then manually transferred tostaining tank assembly 14.

Referring to FIGS. 9-11, device 28 is a tray 78 comprising a vessel tocontain a liquid, gel slab 36 and clamp 52 for manipulating gel 36 froma cassette 26 to clamp 52. In the embodiment illustrated, tray 78 has asubstantially rectangular configuration with a bottom wall 80, sidewalls 82 and end walls 84. Side walls 82 and end walls 84 extend in asubstantially upward direction perpendicular to bottom wall 80 to definean internal cavity 86 with an open top. A retaining arm 88 is coupled toone end wall 84 to engage a gel clamp 52 as discussed hereinafter.

As shown in FIG. 9, bottom wall 80 has a top face 90 and a bottom face92. Bottom face 92 is substantially planar and defines a horizontaldimension of tray 78. Bottom wall 80 includes a first end 94 having afirst bottom section 96 and a second end 98 having a second bottomsection 100. As shown in the embodiment of FIG. 9, a substantiallyinclined middle section 102 extends between first bottom section 96 andsecond bottom section 100. In alternative embodiments, tray 78 can havea substantially flat bottom extending between first end 94 and secondend 98.

First bottom section 96 of bottom wall 80 forms a substantially planarsurface and an area of tray 78 having a substantially uniform depth.Inclined middle section 102 is contiguous with first bottom section 96to form an area of tray 78 having a decreasing depth from first end 94toward second end 96. As shown in FIG. 9, inclined middle section 102has a first end joining first bottom section 96 and a second end joiningsecond bottom section 100. Second bottom section 100 defines a recessedportion 104 that is recessed with respect to inclined middle section102. Recessed portion 104 has a substantially planar bottom surfaceextending between side walls 82.

In preferred embodiments of the invention, first bottom section 96 ofinclined middle section 102 has a surface that resists anelectrophoresis gel from adhering to bottom wall 80. In the embodimentillustrated, inclined section 102 also includes a top surface thatresists adhering to an electrophoresis gel.

In one embodiment of the invention, the top surface of inclined middlesection 102 and the top surface of first bottom section 96 have asurface that is able to support a liquid barrier layer between gel slab36 and the surfaces of tray 78. In the illustrated embodiment, thesurfaces include a plurality of fluid channels 108 formed byspaced-apart projections 110. Projections 110 are spaced-apart to form aplurality of rows and columns to form a substantially uniform array.Projections 110 in the illustrated embodiment have a substantiallypyramid shape formed by outer faces 112 that converge to a peak 114.Projections 110 form channels 108 between adjacent peaks 114, whichappear as a recess or trough. Projections 110 are dimensioned so thatchannels 108 contain an amount of the liquid to form a liquid barrierand to enable peaks 114 to support an electrophoresis gel slab in theliquid without damaging the gel slab 38 as discussed hereinafter ingreater detail. Peaks 114 have a dimension to form a contact area forcontacting the gel that is less than the surface area of top surface 92of bottom wall 80. Projections 110 are spaced apart a distance andprovide a surface area sufficient to support an electrophoresis gelwithout piercing or damaging the gel 36. The spacing between adjacentpeaks preferably prevents the gel from contacting the bottom of channels108. Channels 108 have a width and depth sufficient to contain a volumeof liquid to flow between peaks 114 and prevent an electrophoresis gelfrom adhering to projections 110.

In the embodiment illustrated in FIGS. 9-11, projections 110 havesubstantially planar outer faces 112. In alternative embodiments, theprojections can be formed with concave surfaces or convex surfacesresembling a bubbled surface. In further embodiments, the projectionscan be in the form of spaced-apart ridges forming valleys betweenadjacent peaks. The ridges can be oriented in a longitudinal direction,transverse direction or diagonal direction with respect to alongitudinal dimension of tray 78. In further embodiments, the surfacesof tray 78 can be formed with a series of recesses or channels thatdefine distinct projections as in the illustrated embodiment.

In the illustrated embodiment of tray 78, projections 110 provide asurface that inhibits the gel slab from adhering to the bottom of tray78. The electrophoresis gels as commonly used in the art are soft andpliable. Moreover, the gels generally have a tacky surface that tend tostick to many surfaces on contact. The pliable nature of the gels enablethe gels to stick readily to smooth surfaces such as a glass plate orthe smooth surface of a tray or tank. It has been found that forming thesurface with a plurality of channels, recesses or apertures reduce thesurface area that contacts the gel, and form a liquid barrier therebyinhibiting the gel from sticking and enabling the gel to slide on thesurface without damaging the gel. In addition, the channels provide asystem to prevent or release the suction between the gel and the surfaceof the tray that occurs when the gel is pulled away from the surface.The channels can be of any number of shapes and orientations that areable to release the suction or prevent the suction from forming.Preferably, the channels have a dimension and length to allow a fluid,such as distilled water, deionized water or a buffer solution to flowbetween the gel and the surface of tray 78 to release the suction effectand inhibit the gel from adhering to the surface.

As shown in FIGS. 10 and 11, first bottom section 96 has a dimensioncorresponding substantially to the dimension of an electrophoresis gelcassette 26. Cassette 26 is a standard second dimension electrophoresiscassette as known in the electrophoresis art. Cassette 26 includessupporting plate 34 spaced-apart a uniform distance by spacers (notshown). Plates 34 are typically glass plates, although other materialscan be used. An electrophoresis gel 36 having a thickness of about 2-3mm is provided between plates 34.

Referring to FIG. 10, recess 104 of second bottom section 100 isdimensioned to receive first clamping jaw 54. As shown in FIG. 10,recess 104 is recessed with respect to second bottom section 100 adistance corresponding substantially to the thickness of first clampingjaw 54. In this fashion, the clamping surface of first clamping jaw 54is substantially coplanar with the surface of inclined section 102.

In a preferred embodiment, tray 78 is provided with retaining arm 88 forengaging the operating end of second clamping jaw 56 and retaining theclamping surfaces in an open position as shown in FIG. 10. Retaining arm88 in one preferred embodiment of the invention is connected to an endwall 84 by a pivot pin 116. Pivot pin 116 is fixed to retaining arm 88and extends into an aperture in a top surface 118 of end wall 84. A knob120 is connected to a top end of pivot pin 116 for rotating retainingarm 88 from a retracted position to a retaining position shown in FIG.10. Retaining arm 88 in the embodiment illustrated has a generallyL-shape configuration with a substantially horizontal top leg 122 and adownwardly extending vertical leg 124. Vertical leg 124 has a dimensionto engage the operating end of second clamping jaw 56 as shown in FIG.10.

Tray 78 is used to transfer an electrophoresis gel slab 36 from cassette26 to gel clamp 52. Typically, a liquid 126 such as deionized water,distilled water or a buffer solution is placed in tray 78 to asufficient level to cover projections 110 and cassette 26 as shown inFIG. 10. Cassette 26 is placed in liquid 126 at first bottom section 96of tray 78. The top plate 34 of cassette 26 is gently separated from gel36 in a manner to avoid tearing or distorting gel 36. In one embodiment,cassette 26 is immersed in liquid 126 and the top plate 34 is separatedfrom gel 36 while immersed in liquid 126. In alternative methods, thetop plate can be separated from the gel prior to immersing in theliquid.

Gel clamp 52 is positioned in the recess 104 of tray 78 and secondclamping jaw 56 is pivoted to the open position. Retaining arm 88 isthen rotated to the retaining position to engage second clamping jaw 56and retain clamp 52 in the open position as shown in FIG. 10 forreceiving gel 36. Gel 36 is immersed in liquid 126 and is separated fromthe bottom plate of cassette 26. Gel 36 can then slide upwardly alonginclined middle section 102 to position a longitudinal edge 128 betweenthe clamping surfaces of jaws 54, 56 as shown in FIG. 11. Projections110 provide a small surface area that contacts gel 36 to prevent gel 36from adhering to bottom wall 80 of tray 78. Projections 110 formchannels 108 between adjacent projections to supply the liquid 126 tothe bottom surface of gel 36 so that gel 36 can float and slide alongbottom wall 80. When gel 36 is positioned between clamping-jaws 54 and56, retaining arm 88 is pivoted to the retracted position to allow theclamping surfaces of the jaws to engage gel 36.

Gel clamp 52 serves as a carrier device capable of supporting andsuspending an electrophoresis gel slab without damaging the gel.Electrophoresis gel 36 typically is a conventional gel used intwo-dimensional electrophoresis separation as known in the art. Theelectrophoresis gels are made of an acrylamide material that are about0.5-3 mm thick and can be difficult to handle. Typically the gels areabout 1-1.5 mm thick. The gels are soft and pliable and can tear,stretch and stick to most surfaces that it contacts. Manual handling ofthe gels by conventional methods usually results in a large number ofthe gels being damaged. The gel slab is supported by gel clamp 52 tomanipulate the gel through the various process steps with minimal damageto the gel.

Referring to FIG. 7, clamp 52 has a substantially longitudinal dimensionhaving an operating end 130 and a gripping edge 131. Gripping edge 131is a substantially straight edge and has a length correspondingsubstantially to the length of gel 36. First jaw 54 has a substantiallyplanar configuration and is formed from a sheet material that issufficiently rigid to support a gel slab. Typically, clamp 52 is madefrom a rigid plastic material that is non-reactive with the gel or thevarious solutions used to treat the gel. In alternative embodiments,clamp 52 can be made of metal or other non-reactive materials.

As shown in FIG. 7, operating end 130 of first jaw 54 has a lengthslightly greater than gripping edge 131. Openings 58 in first jaw 52enable coupling to articulated arms of a robotic assembly as discussedhereinafter in greater detail. First jaw 54 has side edges that convergeto gripping edge 131 and form a step portion or shoulder 132 alongopposite sides to engage a support for suspending gel 36 in the liquidcontained in staining assembly 14. In the embodiment illustrated, a rib134 is coupled to a top face of first jaw 54 to define a fulcrum for thesecond jaw 56. Rib 134 is spaced from gripping edge 131 and extendssubstantially the length of first jaw 54 and parallel to gripping edge131.

Second jaw 56 has a longitudinal dimension with a gripping edge 135 andan operating end 136 as shown in FIG. 8. Gripping edge 135 of second jaw56 is a substantially straight edge complementing gripping edge 131 offirst jaw 54 and has a length corresponding to the length of grippingedge 131 of first jaw 54. In the embodiment illustrated, second jaw 56has a width less than the width of first jaw 54. In alternativeembodiments, second jaw 56 can have a width substantially the same as orgreater than the width of first jaw 54. Second jaw 56 is coupled tofirst jaw 54 and is pivotable about rib 134 to open and close thegripping edges of the jaws.

First jaw 54 and second jaw 56 have a longitudinal length to be able togrip and suspend gel 36 without tearing or stretching gel 36. It hasbeen found that continuous griping surfaces of the clamp that extend asubstantial portion of the edge of a gel slab can suspend the gel withlittle or no distortion or tearing. A uniform clamping pressure alongthe length of the gripping edges minimizes distortion and stretching ofthe gel.

First jaw 54 and second jaw 56 are biased by a suitable biasing deviceto apply a sufficient gripping pressure between gripping edges withsufficient force to support an electrophoresis gel slab. Preferably, thejaws are biased to apply a substantially uniform pressure along thelength of the gripping surfaces.

In a preferred form of the invention, first jaw 54 and second jaw 56include several magnets 137 positioned in apertures to bias the grippingedges together. As shown in the embodiment of FIG. 7, magnets 137 arespaced a slight distance from the gripping edges to provide theattracting force to the gripping edges to engage gel slab 36. Magnets137 in the illustrated embodiment are cylindrical bar magnets made froma rare earth metal and are oriented so that opposite poles face eachother to attract the jaws together with a uniform clamping force alongthe length of the jaws sufficient to support a gel without othermechanical coupling devices. In alternative embodiments of theinvention, one or more magnets can be provided on one of the jaws with ametal strip on the other jaw to attract the magnet. A protective plasticfilm or tape can be applied over the apertures in the jaws to retain themagnets in place. In alternative embodiments, the magnets are flexiblemagnetic plastic strips as known in the art that are coupled to the jawsby a suitable adhesive.

In a preferred embodiment, gripping edges 131 and 135 of jaws 54 and 56,respectively, include an abrasive material 138, such as a fine gritsandpaper to assist in gripping gel 36. In preferred embodiments,abrasive member 138 has a length corresponding to the dimensions ofclamp 52 and a width sufficient to grip gel 36 without damaging the gel.In one embodiment of the invention, a resilient member such as is acompressible foam made of a polymeric material is adhesively attached togripping edges of the jaws to assist in applying a uniform clampingpressure along the length of the gel.

The dimensions of the clamp can vary depending on the dimensions of thegel and the robotic assembly. Preferably, the clamps have a grippingedge with a length sufficient to distribute the clamping force along thelength of the gel to prevent the gel from tearing or distorting whensuspended by the clamp. In further embodiments, the clamp can havespaced-apart gripping surfaces that are spaced along the length of thegel to provide the necessary clamping force. Preferably, the grippingsurfaces of the clamps are dimensioned to form a continuous grippingsurface along the length of the gel.

Referring to FIGS. 12-32, staining tank assembly 14 includes a computercontrolled robotic assembly 140 constructed for manipulatingelectrophoresis gel 36 and clamp 52. In the embodiments illustrated,assembly 14 includes several tanks 142 containing various liquids anddefining various work stations for treating and processingelectrophoresis gel 36. Preferably, tanks 142 contain a sufficientamount of a liquid to immerse the gel. Immersing the gel in the liquidsupports the gel to prevent sagging and tearing and prevents the gelfrom drying.

In the illustrated embodiments, robotic assembly 140 is constructed forselectively transferring a plurality of electrophoresis gels tosequential processing stages and particularly through a sequence ofstaining and developing steps using known reactants for electrophoresisgel staining. In one embodiment the staining tanks contain suitablefluorescent dyes and fixing agents. The automated assembly isoperatively connected to the control system and is controlled by thecomputer or microprocessor. The control system monitors and operates theentire assembly and components of the assembly as discussed herein. Thecomputer or microprocessor is operatively connected to the controlsystem and the computer 13 to coordinate processing of the gels inassembly 10. A large number of gels and gel clamps can be placedmanually in a row in one of the tanks. A suitable scanner is moved alongthe row to scan and read the bar codes on each of the gel clamps to takean inventory of the gels in the apparatus. The scanner, feeds theidentifying information from the bar code to the computer to record theinformation of the gels in the tank, record the location of the gels inthe tank and select a staining protocol for-the gels.

The various embodiments illustrated in the drawings generally show asingle electrophoresis gel for purposes of convenience and clarity. Inpractice, the assembly is constructed to receive a large number of gelsthat are continuously carried through the processing tanks according tovarious processing protocols for the gels and are processedsimultaneously or sequentially. The processed gels are ultimatelytransferred to a storage vessel or tank and then transferred to scanningand cutting assembly 16 for subsequent scanning identification, cuttingand analysis of the proteins and other macromolecules in the gel.

Referring to FIGS. 12-15, robotic assembly 140 includes a main supportframe 144 having a length extending substantially the entire length ofapparatus 14. Frame 144 includes an upright vertical support member 146at each end of assembly 14. A bottom rail 148, a middle rail 150 and toprail 152 extend between vertical supports 146. In the embodimentillustrated, rails 148, 150 and 152 are oriented substantiallyhorizontal and extend from an upstream end adjacent loading assembly 12to a downstream end adjacent cutting assembly 16.

Robotic arm assembly 140 includes a vertical rail 154 and a boom 156.Vertical rail 154 is oriented in a substantially perpendicular directionwith respect to bottom rail 148 and extends between bottom rail 148 andtop rail 152. Vertical rail 154 has a bottom end with a bracket thatpreferably supports guide wheels to ride along a top edge of bottom rail148. A top end of vertical rail 154 also includes a bracket having guidewheels 159 to ride along a top side 161 of top rail 152. The bracketswith the guide wheels effectively couple vertical rail 154 from frame144 and are able to guide vertical rail 154 along the entire length ofrails 148 and 152 between the end of frame 144. In one embodiment of theinvention, top rail 152 and bottom rail 148 have a track to receive andguide the wheels along the respective rail.

Frame 144 includes a suitable drive assembly 158 for moving verticalrail 154 along the length of frame 144. Preferably, drive assembly 158is operatively connected to a controller such as a computer ormicroprocessor for selectively controlling the movement and position ofvertical rail 154 with respect to assembly 14 as discussed hereinafterin greater detail. In the embodiment illustrated, drive assembly 158includes a motor 160 having a shaft with a drive gear 162. In thisembodiment, motor 160 is mounted on middle rail 150 at an upstream end.A drive belt 164 extends between drive gear 162 and an idle gear 167 atthe upstream end of middle rail 150. Drive belt 164 can be a continuousbelt that is coupled to vertical rail 154. Motor 160 is actuated tooperate drive belt 164 to move vertical rail 154 along the longitudinallength of frame 144 to a selected position. Preferably, motor 160 is areversible motor that can be controlled to move vertical rail 154 insmall increments. Generally, drive belt 164 has a plurality of teeth forengaging teeth on drive gear 162 to prevent drive belt 164 fromslipping. Drive belt 164 is a flexible belt having sufficient strengthwith limited stretching to effectively move vertical rail 154 alongframe 144 between each end. Other drive assemblies can be used that arecapable of moving vertical with sufficient precision to align boom 156in the desired location. In one embodiment a fixed belt is mounted onthe frame and a gear driven by a drive motor on assembly 140 moves theassembly along the length of the frame.

Boom 156 includes a support housing 166 coupled to vertical rail 154.Vertical rail 154 includes an operating assembly 168 for raising andlowering boom 156 along the length of vertical rail 154. Referring toFIGS. 13 and 14, operating assembly 168 includes a drive motor 170coupled to a rod 172 having external threads. A guide rod 174 isprovided on each side of threaded rod 172 and extends substantiallyparallel to threaded rod 172. Support housing 166 of boom 156 includes athreaded aperture coupled to threaded rod 172 and a pair of axialpassages for receiving guide rods 174 that extend parallel to threadedrod 172. Motor 170 is operated to rotate threaded rod 172 about its axiswhich causes housing 166 to move in a vertical direction along thelength of threaded rod 172. Guide rods 174 are coupled to a top end andthe bottom end of vertical rail 154 to stabilize and guide housing 166along the length of vertical rail 154. Preferably, motor 170 is areversible motor that can be controlled to raise and lower housing 166and boom 156 to the desired position. Typically, threaded rod 172 andguide rods 174 extend the entire length of vertical rail 154.

In the embodiment illustrated in FIG. 14, boom 156 is substantiallyhorizontal and extends outwardly from housing 166. In one embodiment,boom 156 is substantially perpendicular to frame 144. In alternativeembodiments, boom 156 can be oriented at an angle with respect to frame144 depending on the arrangement of the work stations and theconstruction of the overall assembly.

An articulated arm assembly 176 is coupled to boom 156 and includes asuitable drive assembly for selectively moving articulated arm 176 alongthe length of boom 156. Referring to FIG. 14, in one embodiment, boom156 includes a support rail 178 and threaded drive rod 180 having oneend coupled to housing 166. Articulated arm 176 includes a supporthousing 182 having an axial passage for receiving drive rod 180 and anaxial passage for receiving support rail 178.

As shown in FIG. 14, a motor 184 is coupled to support rail 178 andthreaded drive rod 180. Threaded drive rod 180 includes an outer end 186received in a bearing 188 that is coupled to support rail 178 forsupporting the outer end of rod 180. Support housing 182 includes anaxial passage having internal threads complementing the external threadson threaded drive rod 180. Motor 184 is actuated to rotate threadeddrive rod 180 for moving support housing 182 and articulated arm 176along the length of support rail 178 of boom 156. In a preferredembodiment, motor 184 is an electric reversible motor operativelyconnected to a control circuit for selectively controlling the movementof articulated arm 176 in each direction along the longitudinal lengthof support rail 178. Motor 184 is operatively connected to the operatingcomputer.

As shown in FIG. 14, articulated arm 176 includes a main body 190 thatis coupled to support housing 182 and positioned below support rail 178and threaded drive rod 180. Body 190 has a longitudinal dimensionoriented substantially parallel to support rail 178 in the embodimentshown. Two movable coupling arms 192 are pivotally connected to each endof body 190. Coupling arms 192 have a top end coupled to body 190 by apivot pin 194. Coupling arms 192 have a bottom end 196 opposite the topend and include a coupling pin 198.

As shown in FIGS. 17 and 18, an actuator 200 is coupled to body 190 foractuating coupling arms 192. Actuator 200 is provided with connectingrods 202 coupled to each coupling arm 192 for pivoting coupling arms 192inwardly and outwardly with respect to main body 190 from a retractedposition shown in FIG. 17 to an extended position shown in FIG. 18.Actuator 200 in one embodiment of the invention is a pneumaticallyoperated piston assembly that is capable of moving connecting rods 202simultaneously between a retracted position and an extended position formoving coupling arms 192. As shown in FIG. 17, air pressure lines 203extend from a pressure source 205 shown in FIG. 16 to actuator 200.Preferably, the pressure source is computer actuated to automaticallycontrol the arms 192 and to coordinate with the movement with boom 156.In alternative embodiments, actuator 200 can be a solenoid operateddevice, electric motor or other device capable of actuating rods 202.

Referring to FIGS. 12-16, robotic assembly 140 is able to move andmanipulate a work piece in three dimensions or coordinates with respectto tanks 142. Vertical rail 154 can be actuated to move along frame 144oriented in a longitudinal dimension of apparatus 14. Boom 156 moves ina substantially vertical direction with respect to vertical rail 154 andassembly 140. Articulated arm 176 moves in a transverse direction withrespect to apparatus 14 along the length of boom 156. In this manner,articulated arm 176 can maneuver a work piece between various workstations at essentially any location of apparatus 14.

Apparatus 14 of the invention is particularly adapted for manipulatingand staining an electrophoresis gel that is obtained from atwo-dimensional electrophoresis separation process as known in the art.Referring to FIG. 12, tanks 142 are dimensioned to contain a liquid suchas deionized water, distilled water or a buffer solution and a pluralityof electrophoresis gel slabs. As shown in FIG. 16, tanks 142 are formedwith longitudinal sides 204 and a movable frame 206 having a pluralityof spaced-apart notches 208. An electrophoresis gel slab 36 is supportedby a gel clamp 52 having a length to fit within notches 208 of frame 206so that gel 36 is suspended in the liquid contained in tank 142. In analternative embodiment, the top edge of side walls 204 of tank 142 caninclude notches to receive the gel clamp 52. Typically, the notches havea generally V-shaped upper end and slot at the lower end to support thegel clamps.

Robotic assembly 140 is operated to sequentially transfer gels 36 fromtanks 142 to a staining station 210 as shown in FIG. 12. Referring toFIG. 15, clamp 52 is suspended in recesses 208 of frame 206. Articulatedarm 176 is lowered into the position shown to align coupling pins 198 ofarms 192 with the openings 52 in the jaw of clamp 52. Boom 156 is thenmoved toward clamp 52 as shown in FIGS. 19 and 20 to insert couplingpins 198 through opening 58 in clamp 52. In this position, coupling arms192 are in a retracted position so that coupling pins 198 can beinserted through openings in clamp 52. Arms 192 are then pivotedoutwardly to capture clamp 52. Articulated arm 176 can then be raised totransport clamp 52 to the desired location.

Referring to FIGS. 19 and 20, coupling pins 198 have a shaft 212 and aretaining head 214. Head 214 is dimensioned to pass through the openings58 in gel clamp 52 and is dimensioned to retain gel clamp 52 on shaft212 while being maneuvered through the apparatus. Articulated arm 176 ismaneuvered to insert coupling pins 198 through the openings of gel clamp52 and coupling arms 192 are pivoted outwardly to a coupling positionshown in FIG. 18 for coupling to gel clamp 52. Robotic assembly 140 isthen actuated to remove gel 36 and clamp 52 from tank 142 and transfergel 36 to staining station 210. Once the clamp 52 is placed in thedesired position, the arms 192 are retracted and pins 198 are removedfrom clamp 52.

Articulated arm 176 includes a detecting device such as bar code reader215 to read the bar code on clamp 52 as shown in FIG. 19. Reader 215 isconnected to the operating system computer to read bar code 68 on clamp52 to identify and monitor the location of gel clamp 52 throughout thestaining process. Preferably, reader 215 is positioned on an articulatedarm 176 to capture an image and read bar code reader 68 as clamp 52 isbeing captured by articulated arm 176. The operating computer is thenable to identify the gel and select an appropriate staining protocol.Reader 215 is also used to scan the collection of he gel clamps in theapparatus to provide an inventory of the gels. The operating computer isable to monitor the location of the gel to be able to retrieve aspecific gel when desired. Preferably, the reader is required to readthe bar code on the clamp only one time. Once the bar code is read toidentify a gel and gel clamp, the computer records the location of theclamp within the apparatus.

Assembly 14 includes a suitable computer for providing completeautomation of robotic assembly 140. The computer is coupled to the drivemotors to control the operation of each component and coordinate themovement of the assembly. The computer is able to control the operationof each of the motors individually so that the gels can be moved toselected locations. The computer coordinates the movement of the roboticarm and the actuation of the coupling arms to enable the assembly tocapture a gel from one location and transfer the gel to anotherlocation.

Staining station 210 preferably includes a plurality of adjacentstaining tanks 216 as shown in FIG. 12. Each of the staining tanks 216is dimensioned to contain a suitable staining reagent and anelectrophoresis gel. Staining tanks 216 are oriented in a transversedirection with respect to the longitudinal dimension of assembly 14. Thevarious reagents are standard staining reagents as known in the art,such as stains, developing reagents, fixing reagents and rinsingsolutions. Typically, staining tanks 216 contain the various reagentsarranged in the sequence of use. Robotic assembly 140 is provided tosequentially transfer gel 36 to each staining tank 216 for sufficienttime to treat the gel. After a predetermined treatment time, roboticassembly 140 removes gel 36 from one staining tank and transfers gel 36to the next staining tank for the next treatment step according to astaining protocol selected for the gel. The staining reagents and/or thegels are typically agitated continuously to mix the reagents forpromoting uniform staining of the gels. The gels can be moved in an upand down direction to provide a continuous agitation of the reagent.Alternatively, a pump can be provided to circulate the reagents.

In the embodiment shown in FIGS. 12 and 21, staining tanks 216 areassembled as a unit to form longitudinal side walls 218 and end walls220. In a preferred embodiment, a rinse tank 222 containing a rinsewater (not shown) is provided at the downstream end of staining station210. Robotic assembly 140 is programmed to transfer gels 36 at the endof each step of the staining process from a respective staining tank 216to rinse tank 222 for a time sufficient to rinse the reagents from thegel. In embodiments of the invention, robotic assembly 140 is programmedto transfer gel 36 to rinse tank 222 between each processing step torinse the reagents from gel 36 before transferring to the next reagentto minimize contamination of the subsequent reagents by the residue ofthe previous reagent on the gel.

Staining tanks 216 are dimensioned to contain a reagent and anelectrophoresis gel slab by suspending the gel slab in the reagent. Asshown in FIG. 21, staining tanks 216 have side walls 224, end walls 226,and a bottom wall 228. Side walls 224 in the embodiment illustrated aresubstantially vertical and parallel to each other and define a depthsufficient to completely immerse gel 36 in liquid staining reagent 225without gel 36 contacting bottom wall 228. Side walls 224 include a topend 230 that is angled outwardly from the center of staining tank 216 toform inclined surfaces 232. Inclined surfaces 232 open outwardly to forma guide surface for directing a gel into a respective staining tank 216as the gel is lowered by robotic assembly 140.

As shown in FIG. 21, gel 36 is coupled to gel clamp 52 and suspended byframe 206 in a respective staining tank 216. To prevent gel 36 fromadhering to side walls 224, side walls 224 are provided with a texturedsurface to limit the surface area of side walls 224 that contact gel 36.In a preferred embodiment of the invention, side walls 224 are formedwith a plurality of projections 234 extending outwardly from side wall224. Typically, projections 234 are arranged in a substantially uniformarray of rows and columns in a manner similar to the projections of tray78 shown in FIG. 9.

Projections 234 in one embodiment of the invention have a substantiallyrounded shape that form narrow channels between adjacent projections234. The channels have a depth and a width to allow liquid to flowthrough the channels between the projections when gel 36 contacts sidewall 224. Preferably, the channels have a dimension to allow asufficient volume of liquid to flow between gel 36 and side wall 224 andto release the suction effect produced when gel 36 is pulled away fromside wall 224, thereby releasing gel 36 and reducing the risk ofstretching or damaging gel 36.

Preferably, projections 234 have a substantially uniform shape anddimension. In alternative embodiments, the projections can be staggeredin rows and columns and have different lengths or widths. Theprojections typically have a rounded convex surface having a generallydome or bubble shape. In another embodiment, the projections can have aflat top surface separated by V-shaped recesses. In still furtherembodiments, the projections can be substantially parallel ridges havingchannels between adjacent ridges that can be oriented vertically orhorizontally on side walls 224.

Frame 206 forms an agitating assembly to continuously move gels 36within the holding tanks 142 and staining tanks 216. Referring to FIGS.22 and 23, frame 206 includes support rails 236 positioned above a topedge of the side walls, of holding tanks 142 and staining tanks 216 andextend in a longitudinal direction of assembly 14. Support rails 236have a top face 238, an inner face 240 and an outer face. A plurality ofspaced apart notches 208 are formed in inner face 240 and extend to topface 238. Notches 208 have a beveled top surface 244 converging toward aslot 246 at bottom end of notches 242. As shown in FIG. 12, supportrails 236 are positioned on opposite sides of staining tanks 216 andholding tanks 142 with notches aligned with each other. Notches 208 aredimensioned to receive and guide a gel clamp 52 supporting a gel 36 intothe respective slot 246 for suspending gel 36 in a liquid in therespective tank as shown in FIG. 23.

In one embodiment of the invention shown in FIGS. 22 and 23, holdingtanks 142 include a plurality of recesses 248 in side walls 250 ofholding tanks 142. Recesses 248 are spaced between notches 208 of rail236 and adjacent the top edge of side wall 250. A divider 252 isinserted into recesses 248 to form chambers 254 as shown in FIG. 23 to,prevent adjacent gels 36 from contacting each other. As shown in FIG.22, divider 252 has a substantially rectangular shape to conform to theinner shape and dimensions of tank 142 and with outwardly extendingcoupling tabs 256. In the embodiment illustrated, divider 252 is formedfrom two flexible panels 258. Preferably, panels 258 are sufficientlyflexible to be able to bend so that coupling tabs 256 can be inserted orremoved from recesses 248. Each panel 258 preferably has a texturedsurface on the outer face to prevent the gel from adhering to thesurface of divider 252 in a manner similar to the surface of tank 216shown in FIG. 21.

Support rails 236 of frame 206 are mounted for continuous reciprocatingmovement in a vertical direction to move gel 36 within the treatingliquid, thereby continuously agitating the liquid in staining tanks 216and holding tanks 142. In this embodiment, support rails 236continuously reciprocate in a vertical direction, although inalternative embodiments, support rails 236 can oscillate in a horizontaldirection to continuously agitate the reagent. Continuous agitation ofthe gels and the reagent in staining tanks 216 provide for a moreuniform distribution of the liquid and substantially uniform temperaturethroughout the surfaces of gel 36 during the staining steps.

Referring to FIGS. 24 and 25, each support rail 236 is coupled to aforward and trailing L-shaped actuating lever 260. Each lever 260includes a body portion 262 having a top leg 264 extending substantiallyperpendicular to body 262. Leg 264 has an outer end 266 having a pivotpin 268 coupled to rails 236. A top end of body 262 is pivotally coupledby a pivot pin 270 to a fixed support 272 on the respective tank.

Actuating levers 260 are coupled to the respective support rail 236 oneach side of the tank and are connected together by a connecting rod 274extending between the body portion 262 of each actuating lever 260. Inthis manner, the pivoting levers are connected together to move inunison so that each support rail 236 reciprocates simultaneously. Atleast one of the levers 260 is connected to a drive motor 276. Drivemotor 276 is mounted to a fixed support 278 and includes aneccentrically mounted crank 280. A connecting arm 282 has one endpivotally connected to crank 280 and an opposite end pivotally connectedto a lever 260 on each side of the respective tank. As shown in FIGS. 24and 25, motor 276 is actuated to rotate crank 280 to produce a pivotingmovement of levers 260 about the respective pivot points 270. Thepivotal movement of levers 260 result in a reciprocating motion ofsupport rails 236 in a substantially vertical direction. Motor 276 isconnected to a suitable power source and can be controlled by amicroprocessor or the operating computer to control the timing, speed ofmotor 276 and the desired sequencing of the agitation of the respectivegel and reagent.

In another embodiment, a liquid circulation system can be included inthe tanks 142 and in each of the staining tanks 216 to provide a uniformdistribution and temperature of the liquid. In this embodiment as shownin FIGS. 26 and 27, a liquid treating tank, such as holding tank 142,includes a pump 284 having an intake connected to an intake tube 286 andan outlet connected to an outlet tube 288. Intake tube 286 has an endpositioned below the surface of liquid 290 in tank 142 to withdrawliquid 290 from the tank. The outlet tube 288 extends along the bottomof tank 142 in a circular pattern as shown in FIG. 27. Preferably,outlet tube 288 includes a plurality of outlet openings 292 along thelength of the portion submerged in the liquid 290. Pump 284 continuouslywithdraws liquid 290 from an upper level and recirculates the liquidalong the bottom to provide a uniform distribution of the reagents andto provide a uniform temperature throughout the liquid. In oneembodiment, the liquid can be passed through a suitable heating orcooling device to adjust and monitor the temperature of the treatingliquid as needed.

In embodiments of the invention, a robotic assembly 140 is programmed toselect a gel from a staining tank 216, transfer the gel to rinse tank220 for a predetermined period of time, and then transfer the gel to adeveloping tank where an image of the gel can be captured at differentstages of the developing step. After one or more images of the gel arecaptured, robotic assembly 140 returns the gel to the staining tank 216for further processing. The gel is again transferred to the developingtank after further processing to obtain a sequence of images for the gelduring the staining process. Robotic assembly 140 is capable ofsequentially transferring several gels between the various tanks forcapturing sequential images of several gels. The computer control systemof robotic assembly 140 maintains a record of the location of each gelbeing processed, the stage of the process for each gel and coordinates acaptured image with the particular gel.

During the processing of the electrophoresis gels in the varioustreating liquids, the gels can shrink or expand slightly in one or moredimensions, which can result in some distortion of the gel with respectto the clamp. In some embodiments of the invention, robotic assembly 140transfers the gels 36 and the clamps 52 to an apparatus 300 that is ableto open the clamping jaws, allow the gels to relax and close theclamping jaws on the relaxed gels. By opening the clamping jaws, thestresses formed in the gel between the clamping surfaces can berelieved.

In one embodiment of the invention, apparatus 300 is used in conjunctionwith holding tanks 142 and staining tanks 216 that contain a treatingliquid. In this embodiment, apparatus 300 is coupled to side rails 236of frame 206. Alternatively, apparatus 300 can be coupled directly tothe top edge of the side walls of a tank.

Referring to FIGS. 28 and 29, apparatus 300 includes a first operatingarm 302 and a second operating arm 304 that are parallel and spacedapart a distance to receive gel clamp 52 and gel 36 therebetween. Firstarm 302 has a top end 306 connected to a support rod 308. Support rod308 has outer ends 310 that are pivotally connected to a first endmember 312 and a second end member 314. Second arm 304 has a top end 316connected to a support rod 318 having outer ends 320. Outer ends 320 ofsupport rod 318 are pivotally connected to first end member 312 andsecond end member 314.

First end member 312 is substantially parallel to second end member 314.First arm 302 is substantially parallel to second arm 304 to form asubstantially rectangular shaped structure. Referring to FIGS. 28 and29, first end member 312 has a plate 322 having spaced apart apertures324 and 326 to receive end 310 of support rod 302 and end 320 of supportrod 318, respectively. A coupling member 328 is provided at eachlongitudinal end of first end member 312 for coupling first end member312 to a respective side rail 336 of frame 144. Second end member 314 issubstantially a mirror image of first end member 312 and includes aplate 330 having spaced apart apertures 332 and 334 and a couplingmember 336 at its longitudinal ends. Apertures 332 and 334 receive theend 310 of support rod 308 and the end 320 of support rod 318,respectively, for allowing pivotal movement of first arm 302 and secondarm 304 with respect to end members 312 and 314.

Referring to FIGS. 30A-30B, support rod 308 of first operating arm 302includes an upwardly extending connecting arm 336 adjacent first endmember 312. Connecting arm 336 has a top end 338 with an aperture 340for receiving a connecting pin 342. As shown in FIG. 30A, connecting arm336 is oriented substantially parallel to the plane of first arm 302.Support rod 318 of second operating arm 304 includes a connecting arm344 extending in an upward direction. Connecting arm 344 includes a topend 346 having an aperture 348 for receiving a pin 350.

An actuator 352 is coupled to connecting arm 336 and connecting arm 344to pivot first arm 302 and second arm 304. In the embodimentillustrated, actuator 352 includes a pneumatic cylinder 354 having areciprocating piston connected to a rod 356. Pneumatic cylinder 354 ispivotally connected to connecting arm 3,44 by pin 350. Rod 356 has anouter end 358 connected to connecting arm 336 by pin 342. Pneumaticcylinder 354 is connected to a pressure source by lines 360 toreciprocate rod 356 with respect to cylinder 354 to pivot connectingarms 336 and 344 for pivoting first arm 302 and second arm 304. Pressurelines 360 are coupled to a suitable pressure source such as a pump 362.A microprocessor or a computer 364 controls and actuates pump 362 inselected sequences to operate assembly 300. Computer 364 is connected toa main computer which controls a robotic assembly 140 to coordinate themovement of robotic arm 176 and the location of the gel clamp and itsassociated gel. In alternative embodiments, actuator 352 can be ahydraulically operated, solenoid operated or electrically operateddevice or other suitable device for actuating the apparatus.

As shown in FIGS. 30A-30B, apparatus 300 is positioned on top of rails236, and gel clamp 52 is positioned between first arm 302 and second arm304 so that gel 36 is suspended in the treating liquid. The treatingliquid can cause gel 36 to exhibit some shrinking or expansion, whichcan cause gel 36 to distort and twist when gel clamp 52 does not allowgel 36 to move. In this embodiment of the invention, pneumatic cylinder354 is actuated to pivot first arm 302 and second arm 304 apart fromeach other so that gel clamp 52 can be lowered by robotic arm 176 intoposition on rails 236 and supported in the slots between arms 302 and304 as shown in FIG. 30A. Pneumatic cylinder 354 is then actuated topivot first arm 302 and second arm 304 toward each other so that thearms grip gel 36 below gel clamp 52 as shown in FIG. 30B and engage gelclamp 52 to open the clamping jaws and allow gel 36 to expand orcontract to its normal position as shown in FIG. 30C. First arm 302 andsecond arm 304 are then pivoted outwardly to release gel 36 and gelclamp 52 so that gel clamp 52 again closes on gel 36 as shown in FIG.30D.

Referring to FIG. 30A, first end member 312 includes stop members 366 oneach side of connecting arm 344 to limit the pivotal movement ofconnecting arm 344. Preferably, stop members 366 are oriented to limitthe pivotal movement of second arm 304 to a substantially verticalorientation when pivoted inwardly toward first arm 302.

First clamping arm 302 has a lower end 368 opposite top end 306. Arocker arm 370 is connected to lower end 368 of first arm 302 in amanner to allow limited pivotal movement of rocker arm 370 with respectto first arm 302. Rocker arm 370 has a longitudinal length substantiallyequal to the length of first arm 302 with a bottom edge 372 and a topedge 374. Rocker arm 370 is pivotally connected to lower end 368 offirst arm 302 by screws 376 or other suitable fastening members. Screws376 extend through a respective aperture 378 in rocker arm 370 that arespaced from top edge 374. Screws 376 are threaded into complementingapertures 380 in first arm 302. Preferably, apertures have a diameterslightly greater than the diameter of screws 376 to provide limitedpivotal movement of rocker arm 368 with respect to first arm 302.

Bottom edge 372 of rocker arm 370 defines a gripping surface 382 forgripping gel 36. Preferably, a rib 384 extends along bottom edge 372 andextends outwardly from the plane of rocker arm 370. Rib 384 can beintegrally formed with rocker arm 370 or a separate element coupled torocker arm 370 by an adhesive or mechanical fastener. Top edge 374 ofrocker arm 370 defines an actuating surface for engaging gel clamp 52.In one preferred embodiment, a rib 386 extends along top edge 374 ofrocker arm 370 to define actuating surface 388.

In preferred embodiments, rib 384 and rib 386 extend the length ofrocker arm 370. Rib 384 has a width sufficient to grip and support thegel 36. Typically, rib 384 extends outwardly from the face of rocker arm370 a distance to enable rib 384 to grip gel 36 without rocker arm 370interfering with gel clamp 52.

Second arm 304 in the embodiment illustrated has an actuating member 390having a substantially planar configuration. Actuating member 390 has abottom end 392 and a top end 394. Bottom end 392 defines a grippingsurface 396 for gripping gel 36. In a preferred embodiment, bottom end392 of actuating member 390 includes a rib 398 defining gripping surface396. As shown in FIGS. 30A-30D, rib 398 is aligned with rib 384 ofrocker arm 370 for gripping opposite sides of gel 36. Preferably, rib398 extends outwardly from the face of actuating member 390 a distanceat least equal to the thickness of the clamping jaw of gel clamp 52 toenable rib 398 to grip gel 36 without interference from gel clamp 52.Actuating member 390 can be coupled to second arm 304 by screws or otherfasteners. Alternatively, actuating member 390 and second arm 304 can beintegrally formed as a one-piece unit. In one embodiment of theinvention, gripping surfaces 382 and 398 include a textured surface,such as a fine grit sandpaper to provide a slip resistant surface.

In the illustrated embodiments, first arm 302 and arm 304 are mounted topivot about a fixed pivot point. In other embodiments the arms aremounted to move in a substantially linear direction rather that in apivotal motion. The actuating members and the operating arms are coupledto the support to reciprocate first arm 302 and second arm 304 towardeach other in a linear motion.

Referring FIGS. 30A-30D, the method of the invention for relievingtension in gel 36 is depicted. As shown in FIG. 30A, pneumatic cylinder354 is actuated to pivot first arm 302 and second arm 304 outwardly sothat gel 36 and gel clamp 52 can be lowered into position between firstarm 302 and second arm 304. Pneumatic cylinder 354 is then actuated topivot first arm 302 and second arm 304 toward each other so that therespective gripping surfaces contact opposite sides of gel 36 withsufficient pressure to grip gel 36. As shown in FIG. 30B, second arm 304is in a substantially vertical orientation with connecting arm 344engaging stop member 366. Further actuation of pneumatic cylinder 354continues to pivot first arm 302 toward second arm 304 into engagementwith gel clamp 52 in the position shown in FIG. 30C.

The pivotal movement of first arm 302 enables rocker arm 370 to pivotwith respect to first arm 302 so that actuating surface 388 engages atop end of the clamping jaw to pivot the clamping jaw about its fulcrum,thereby separating the gripping surfaces of gel clamp 52 from gel 36. Inthis position, gripping surface 382 of first arm 304 and grippingsurface 396 of second arm 304 hold gel 36 in position until the clampingjaws of gel clamp 52 are again closed to grip gel 36. As shown in FIG.30C, rib 386 extends from rocker arm 370 a distance sufficient to allowlimited pivotal movement of the clamping jaw of gel clamp 52, therebyallowing gel clamp 52 to open. The method steps can be repeated severaltimes as necessary to relieve stresses with respect to gel clamp 52 thatis caused by contraction or expansion of gel 36. As shown in FIG. 30D,pneumatic cylinder 354 is again actuated to separate first arm 302 andsecond arm 304 to enable gel clamp 52 and gel 36 to be removed fromassembly 300.

FIGS. 31 and. 32 show another embodiment of the invention where anactuating assembly 402 is constructed to open the clamping jaws of gelclamp 52 to separate gel 36 completely from gel clamp 52 afterprocessing gel 36. Assembly 402 is typically used only when the gel isto be discarded at the end of the process. In one embodiment shown inFIG. 13, assembly 402 is provided at the upstream end of roboticassembly 140.

Referring to FIG. 31, assembly 402 includes opposite end members 404having a recess 406 for receiving gel clamp 52. A first arm 408 ispivotally connected to end members 404 by a pin 410. A second arm 412 isalso pivotally connected to end members 404 by a pin 414. First arm 408has a top end 416 and a lower end 418. Lower end 418 defines anactuating surface 420 for actuating gel clamp 52. In the embodimentillustrated, lower end 418 of first arm 408 includes a flat surfacedefining actuating surface 420.

Second arm 412 includes a top end 424 and a lower end 426 that opposesfirst arm 408. Lower end 426 defines an actuating surface 428. As shownin FIG. 31, lower end 424 of second arm 418 includes a rib 430 definingactuating surface 428. Top end 416 of first arm 408 and top end 424 ofsecond arm 412 are operatively coupled to an actuator 432. Actuator 432in this embodiment is a pneumatic cylinder 434 connected to second arm412. Pneumatic cylinder 434 includes a reciprocating piston rod 436connected to first arm 408.

Actuating surface 420 of first arm 408 and actuating surface 428 ofsecond arm 412 are oriented to engage the clamping jaws of gel clamp 52.Actuator 432 is operated to pivot first arm 408 and second arm 412 sothat the respective actuating surfaces engage gel clamp 52 withsufficient force to open the clamping jaws allowing gel 36 to fall fromgel clamp 52 to a suitable waste receptacle 438. Gel clamp 52 can thenbe reused with a new gel for processing.

After the gels 36 are stained in the various staining tanks 216, roboticassembly 140 transfers the gels to one of the holding tanks 142. Holdingtanks 142 typically contain a liquid, such as a deionized water, toprevent the gel from drying. In addition, the liquid supports the gel toprevent the gel from sagging or tearing under its own weight. Typically,the gels remain in the holding tank until gels are ready to be scannedand the selected protein spots are cut from the gel.

The gels 36 and the gel clamp 52 are sequentially transferred from therobotic assembly 140 for staining gels to cutting assembly 16 as shownin FIG. 1 and FIGS. 33-52. As shown in FIG. 33, cutting assembly 16includes a robotic assembly 450 for manipulating the gels 36, scanningand imaging devices 452, and gel cutting apparatus 454. In theillustrated embodiment, two gel scanning and imaging devices 452 and twogel cutting devices are shown, although the actual number of devices canvary depending on the desired throughput of the assembly. A gel relaxingdevice 710 is also provided to level and flatten the gel as discussedhereinafter in greater detail.

Referring to FIG. 33, robotic assembly 450 is a computer controlledassembly having a robotic arm 456 pivotally coupled to a base 458. Base458 is mounted on a movable horizontal support rail 460. Support rail460 has opposite ends 462 coupled to vertical supports 464. A cross bar466 as shown in FIG. 33 extends between the top ends 468 of verticalsupports 464 to stabilize vertical supports 464 and robotic assembly450.

Robotic arm 456 of assembly 450 is movable in vertical and horizontaldirections to manipulate gel 36 from the staining assembly 14 toscanning device 452 and gel cutting apparatus 454 as discussedhereinafter in greater detail. As shown in FIG. 35, a motor 470 ismounted on vertical support 464 and is coupled to horizontal rail 460for moving horizontal rail 460 along a vertical axis of vertical support464. In one embodiment of the invention, motor 470 is operativelyconnected to a drive pulley 472 to drive a continuous cable 474, belt orother drive member. The cable 474 is in turn coupled to horizontalsupport rail 460. Motor 470 is actuated to drive the cable 474 to raiseand lower the horizontal support rail along a vertical track 476extending the height of vertical supports 464 as shown in FIG. 35.

Referring to FIGS. 34-38, robotic arm 456 is pivotally connected to base458 by pivot shaft 478 extending outwardly from base 458. Base 458includes a drive assembly, shown as motor 480 for moving base 458 alongthe length of horizontal support rail 460 between vertical supports 464.Motor 480 is connected to a drive assembly, such as a drive belt forselectively moving base 458 and robotic arm 456 along horizontal supportrail 460. Motor 480, which can be electrically operated or pneumaticallyoperated is operatively coupled to an operating computer to control themovement and timing of base 458.

An operating motor 482 for pivoting robotic arm 456 is mounted on base458. Motor 482 is operatively connected to a pivot shaft 478 to pivotrobotic arm 456 about an axis perpendicular to base 458 and horizontalsupport rail 460. Motor 482 is typically an electric motor that isoperatively connected to the operating computer.

FIG. 34 is a top view of robotic assembly 450 showing robotic arm 456 ina vertical position and showing the robotic arm 156 of staining assembly14. Robotic arm 456 includes an operating arm 484 coupled to pivot shaft478 and oriented substantially parallel to base 458. A support arm 486is coupled to operating arm 484 and extends in a direction substantiallyperpendicular to operating arm 484. Support arm 486 has a lengthsufficient to support gel 36 and a support tray 488 shown in FIG. 38 asdiscussed hereinafter in greater detail.

Referring to FIG. 35, support arm 486 has a body portion with a bottom492 and a flange 494 extending outwardly from bottom edge 492. Flange494 is spaced from a front side 496 of support arm 486 a distance todefine a ledge 498. In the illustrated embodiment, ledge 498 and flange494 have a length corresponding substantially to the length of supportarm 486. Preferably, ledge 498 and flange 494 have dimensions to receiveand support tray 488. Trya 488 forms a supporting member for supportinga gel during scanning and cutting of the gel.

As shown in FIGS. 36 and 37, flange 494 includes a substantiallyU-shaped slot 500 having an open end along a bottom edge 502 of flange494. In the embodiment shown, slot 500 is positioned in the middle offlange 494. A proximity switch 584 is provided on flange 494 to detectthe presence of a tray 488. A locking pin 504 extends through slot 500for reciprocal movement toward ledge 498 within slot 500. Locking pin504 includes a shaft 506 and an enlarged head 508 for coupling to tray488 as shown in FIGS. 35 and 38.

Referring to FIG. 37, shaft 506 of locking pin 504 is coupled to a leverarm 510 at a first end 512. Lever arm 510 is pivotally coupled to afixed pivot pin 514 at a middle section between first end 512 and asecond end 516. Lever arm 510 pivots about pin 514 to move locking pin504 within slot 500 toward ledge 498. An operating assembly 518 iscoupled to second end 516 of lever arm 510 to pivot lever arm 510 aboutpin 514.

Operating assembly 518 in one embodiment of the invention shown in FIG.37 includes a pneumatic cylinder and piston assembly 520 for selectivelymoving a piston rod 522. Piston rod 522 has an operating end 524 coupledto an operating linkage 526. Operating linkage 526 includes a first arm528 having a first end 530 pivotally coupled to operating end 524 ofpiston rod 522 and a second end 532 pivotally coupled to arm 486 by afixed pivot pin 534. Operating linkage 526 includes a second arm 536having a first end 538 pivotally coupled to operating end 524 of pistonrod 522 and second end 540 pivotally coupled to lever arm 510. Pneumaticcylinder 520 includes air supply conduits 541 extending to a pressuresource 542 shown in FIG. 35 for selectively supplying air pressure tocylinder 520 to move piston rod 522 in the desired direction.

Referring to FIG. 37, pneumatic cylinder 520 is actuated to extendpiston rod 522 outwardly. As piston rod 522 moves outwardly, linkagearms 528 and 536 move second end 516 of lever arm 510 downwardly causinglever arm 510 to pivot about pivot pin 514. The pivotal movement oflever arm 510 moves end 512 and locking pin 504 upwardly into a lockingposition.

As shown in FIGS. 38-40, tray 488 is dimensioned to support a gel 36 andthe gel clamp and to cooperate with scanner assembly 452 and gel spotcutter assembly 454. Referring to FIG. 39, tray 488 in one embodiment ofthe invention has a substantially rectangular shape with parallel sideedges 542, a first end 544 and a second end 546. First end 544 of tray488 includes a handle portion 548 extending outwardly substantially inthe plane of tray 488. As shown in FIG. 39, handle 548 has a widthslightly less than the overall width of tray 488. Handle 548 in theembodiment illustrated includes two spaced-apart apertures 550 having acircular configuration with a beveled edge 552. Apertures 550 can beprovided in handle 548 for mounting tray 488 on a suitable storagehanger or robotic device.

A triangular shaped aperture 554 having a beveled edge 556 is formed inhandle 548. Preferably, aperture 554 is centrally located in handle 548.Triangular shaped aperture 554 is dimensioned to cooperate with alocking pin 504 of robotic arm 456 for transferring tray 488 and theassociated electrophoresis gel between various work stations. Triangularshaped aperture 554 is oriented with its apex 558 positioned toward anouter edge 560 of handle 548 and with its base 562 spaced inwardly fromthe outer edge 560.

Tray 488 includes a recessed area 564 at first end 544 extending betweenside edges 542. As shown in FIG. 39, recessed area 564 has asubstantially planar surface with a notched portion 566 adjacent eachside edge 542. Two spaced-apart openings 568 are provided in recessedarea 564. In the embodiment illustrated, openings 568 have asubstantially rectangular configuration.

Referring to FIG. 39, notched portions 566 have a U-shaped recess 570,an inclined face 572 and a flat top portion 574 extending substantiallyperpendicular to the bottom wall of recessed area 564. Flat top portion574 is dimensioned to support a gel clamp as shown in FIG. 38.

In the embodiment illustrated, side portions 576 extend inwardly fromthe respective side edge 542. A flat plate member 578 is coupled to sideportions 576 on a top surface thereof. As shown in FIG. 39, plate 578 iscoupled to the top face of the body of tray 488 to define recessed area564. Plate 578 is generally made of glass or other material to enablescanning and imaging of the gel.

In one embodiment of the invention, side portions 576 of tray 488 areprovided with a plurality of spaced-apart ridges 580 that are orientedat an acute angle with respect to the respective side edge 542. As shownin FIG. 39, ridges 580 are oriented at an angle of about 45° and extendfrom the respective side edge 542 toward second end 546 of tray 488.Ridges 580 terminate a short distance from a side edge 582 of plate 578.Ridges 580 are oriented to direct a washing liquid from side edges 542of tray 488 toward plate 578 when tray 488 is suspended vertically.Ridges 580 enable a rinse liquid to drain away from side edges 542 whensuspended vertically to minimize the amount of the rinse liquidremaining on side edges 542 which can be transferred to guide rails ofcutting apparatus 454.

Plate 578 is dimensioned to support an electrophoresis gel obtained froma two dimensional electrophoresis separation process as known in theart. Plate 578 is substantially flat and has a planar top surface forsupporting the gel. As shown in FIG. 39, plate 578 has side edges 582that overlie side portions 576 for coupling plate 578 to side portions576. In a preferred embodiment of the invention, plate 578 is made froma flat sheet of glass. Tray 488 is typically made of metal having acorrosion resistant and non-reactive finish to prevent contamination ofthe electrophoresis gel and reagents that may contact tray 488.

Referring to FIG. 40, tray 488 is dimensioned to support a gel 36 andthe gel clamp 52. The gel clamp fits in recessed area 564 of tray 488with the shoulders of the gel clamp engaging top surface 574 of notches566. Recessed area 564 preferably has a depth correspondingsubstantially to the thickness of the clamping jaw of the gel clamp sothat gel 36 can lay flat on plate 578.

Robotic assembly 450 is positioned to cooperate with the roboticassembly 140 of staining assembly 14. As shown in FIGS. 33 and 34, theguide rails 144 of robotic assembly 140 overlap with robotic assembly450 so that the robotic assemblies are able to transfer a gel and gelclamp between the robotic assemblies.

As shown in FIG. 38, a tray 488 is captured by robotic arm 486 byinserting locking pin 504 through aperture 554 of tray 488. Pneumaticcylinder 520 is actuated to move locking pin 504 from the unlockedposition to the locked position toward ledge 498 to draw tray 488 into atight clamping engagement with ledge 498. A proximity switch 584 onflange 494 is contacted by tray 488 to detect when tray 488 is securedto arm 456. Proximity switch 584 is connected to the central operatingcomputer to control the operation of robotic arm 456.

Once robotic arm 456 captures tray 488, robotic arm 456 is moved intothe position shown in FIG. 34 for cooperating with the robotic arm 156of robotic assembly 140 of staining tank assembly 14. Referring to FIGS.41-43, robotic arm 456 is pivoted to position tray 488 at an incline.Typically, tray 488 is oriented at an angle of about 700 to about 850from the horizontal position. Robotic arm 156 of staining tank assemblycarries a gel 36 with a gel clamp 52 and is moved slowly toward tray 488as shown in FIGS. 41-43. Preferably, gel 36 is aligned with plate 578 oftray 488 and moved into contact so that the bottom end of the suspendedgel 36 contacts tray 488 as shown in FIG. 42. The robotic arm 156continues to move toward tray 488 until the entire gel is placed onplate 578 and the gel clamp 52 is positioned in recessed area 564 oftray 488. The operating arms of robotic assembly 140 are retracted andthe robotic arm is moved away from tray 488 to release the gel clamp andtransfer the gel and gel clamp to tray 488. In the illustratedembodiment, the tray 488 is held stationary while the gel and gel clampare moved toward tray 488. In alternative embodiments, the gel can beheld stationary and tray 488 can be moved into contact with the gel.Preferably the gel is loose on the tray and the wet surface of the gelenables the gel to adhere or stick to the plate without the need to bondor otherwise fix the gel to the tray.

Once the gel and gel clamp are captured on tray 488, robotic arm 456 ispivoted to orient tray 488 in a substantially horizontal position asshown in FIG. 44. The gel 36 when placed on plate 578 typically capturesair bubbles between the gel and plate 578. In preferred embodiments, itis desirable to remove air bubbles to enable the gel to lay flat on tray488. Depending on the size and location of the trapped air bubbles, thebubbles create an uneven surface on the gel which can interfere with thescanning of the gel and the cutting of selected spots from the gel.

In one embodiment of the invention, the gel clamp 52 is opened while thetray 488 is oriented in the horizontal position to allow the gel torelax and to enable the air bubbles to escape. A vertical bar can bepositioned above robotic arm 456 so that when horizontal support rail460 is then moved upward, the bottom end of the bar contacts and opensthe jaws of the gel clamp 52. Tray 488 is maintained with the jaws ofthe gel clamp open for a time sufficient to enable the gel to lay flatand the air bubbles to escape from between the gel and plate 578. Inother embodiments, tray 488 can be raised and lowered several times toopen and close the jaws of the gel clamp repeatedly to enable the airbubbles to escape.

After gel 36 and the gel clamp are positioned on tray 488, robotic arm456 is moved to a position for inserting tray 488 into scanner 452 asshown in FIG. 46. Robotic arm 456 supports tray 488 in a horizontalposition and aligns tray 488 with the opening of the scanner 452.Robotic arm 456 and base 458 are moved along horizontal support arm 460to insert tray 488 and gel 36 into scanner 452 as shown in FIG. 47.Locking pin 198 is moved outwardly and robotic arm 456 releases tray 488to leave tray 488 in scanner 452 during the scanning process as shown inFIG. 48 while robotic arm 456 can proceed to capture a second tray andrepeat the process. Robotic arm 456 is programmed to move locking pin198 to the unlocked position and then move downwardly to remove pin 198from tray 488. At the end of the scanning cycle, robotic arm 456captures tray 488, withdraws tray 488 from scanner 452 and transferstray 488 to gel spot cutter 454 as shown in FIG. 49. Robotic arm 456 isthen available to capture another tray and gel which can be delivered toa scanner or gel cutting device.

Scanner 452 is typically a commercially available scanning and imagingdevice used for electrophoresis gels to identify the locations ofproteins in the gel. The scanner illuminates the gel and captures animage of the stained gel spots on the gel. The scanner then compares theimage with a library of images from known proteins or biological samplesusing known software programs. Scanner 452 is operatively connected tothe operating system and computer to identify the stained protein spotsand to target certain protein spots according to the selected processingprotocol. The information obtained from the scanning, imagingidentification and targeting of the protein is stored in the computerand transferred to gel spot cutter 454 in the form of excising orcutting instructions to cut selected spots from the gel. The imagesignal from the scanner is processed in the computer of the controlsystem and generates a cutting signal for directing and controlling spotcutting assembly 454. The control system is connected to the scanner andreceives a signal from the scanner indicating completion of the scanningcycle. The control system actuates robotic arm assembly 592 to capturethe tray 488 in the scanner, remove the tray from the scanner andtransfer the tray to cutting assembly 454.

In the illustrated embodiment, several scanning devices 452 and gel spotcutting assemblies 454 are placed on a shelf unit in a stacked relationto enable processing of several gels simultaneously. The actual numberof the scanning devices and gel spot cutting devices can depend on thedesired throughput of the system.

Cutting assembly 454 as shown in FIG. 50 includes a housing 590supporting a robotic arm assembly 592. Housing 590 includes a base 594defining a work surface with side walls 596 and an open front end 598.

Base 594 includes a pair of spaced-apart guide rails 600 for receivingtray 488. Guide rails 600 have an upright section and an inwardlyextending flange to contain tray 488 and to allow robotic arm 484 toslide tray 488 into and out of the cutting position shown in FIG. 50. Inone embodiment of the invention, base 594 includes a recessed areabetween guide rails 600 to receive tray 488. The recessed area has adepth corresponding substantially to the thickness of tray 488 so that atop edge of tray 488 is substantially in the same plane as base 594.

Robotic arm assembly 592 is mounted on base 594 for movement in adirection substantially parallel to base 594. Robotic arm assembly 592includes a motor 602 attached to base 594 of housing 590 adjacent therecessed area. A first movable arm 604 has a first end 606 operativelyconnected to motor 602 for pivoting first arm 604 about an axissubstantially perpendicular to the plane of base 594. First arm 604 hasa second end 608 having a second motor 610 coupled thereto. A second arm612 has a first end 614 operatively coupled to second motor 610 forpivoting about an axis of second motor 610 parallel to the axis ofrotation of first motor 602. Second arm 612 includes a second end 616having a cutting head assembly 618 for excising a sample from anelectrophoresis gel.

Robotic arm assembly 592 is operatively connected to a computer fordirecting the movement of first and second arms 604 and 612,respectively, as well as cutting head assembly 618. The computerprocesses the signals from scanner 452 and generates a signal foractuating first motor 602 to pivot first arm 604 about the axis of motor602 in the direction of arrow 620. Simultaneously, the computer producesa signal to actuate second motor 610 to rotate the second arm about theaxis of motor 610 in the direction of arrow 622. The controlled movementof motors 602 and 610 move cutting head assembly 618 to a selectedposition with respect to an electrophoresis gel on tray 488 for excisinga selected sample from the gel. In a preferred embodiment of theinvention, the computer receives the imaging signal from scanning device452, processes the signal to identify the selected locations on theelectrophoresis gel, and produces a cutting signal based on polarcoordinates for excising the sample from the gel. In alternativeembodiments, the computer can generate a cutting signal to directrobotic arm assembly 592 based on XY coordinates.

In one embodiment, one guide rail 600 includes a spring biased detent644 to engage a recess of tray 488 to position tray 488 in a specificlocation in cutting assembly 454. In one embodiment of the invention,detent 644 is a spring biased, pivotally mounted arm 646 having a rollerthat allows tray 488 to be inserted and removed from guide rails 600.Preferably, detent 644 includes a microswitch 648 which is operativelyconnected to the computer and produces a positioning signal to indicatethat tray 488 is properly positioned in cutting assembly. Once tray 488is properly positioned in cutting assembly as indicated by microswitch648, the computer actuates robotic arm assembly 592 to cut and transferthe gel spot to the microtiter plate 624.

Cutting head 618 can be any suitable device capable of excising aselected portion of the gel and transferring the excised portion to amicrotiter plate 624. In one embodiment of the invention, the cuttinghead includes a pneumatic cylinder having a retractable piston rod. Thepiston rod is coupled to and reciprocates a supporting block thatincludes an internal passage having a bottom end, a cylindrical internalcavity and a supply passage. A hollow tubular cutting punch extendsdownwardly from bottom end of the supporting block and is incommunication with the cavity and the internal passage. The cuttingpunch reciprocates to cut and remove a section of the gel. Cutting punchcan include an internal piston or fluid pressure source to eject the cutgel spot from the punch into the appropriate well of the microtiterplate.

In operation, cutting head 618 is positioned above the gel to excise thesample identified by scanning and imaging device. The cutting head 618is actuated to cut and remove a gel sample from the gel on tray 488. Therobotic arm assembly then moves the cutting head 618 to a positiondirectly above a selected well 626 of a microtiter plate 624 and the gelsample is ejected. In a preferred embodiment, a wash liquid such asdeionized water is introduced through a supply conduit which flowsthrough the cutting punch to assist in ejecting the cut gel piece fromthe punch and to wash any residue from the punch. The sequence isrepeated until each identified sample is cut from the gel andtransferred to a respective well in a microtiter plate.

Robotic assembly 592 is primarily programmed and operated by thecomputer to excise selected portions or samples from the gel andautomatically transfer the excised portion to a sample receivingmicrotiter tray 624. As shown in FIG. 50, microtiter plate 624 is astandard multiwell sample plate as known in the art. Plate 624 typicallyhas a substantially rectangular shape with a top face and side walls. Aplurality of spaced-apart wells 626 are formed in the top face and aredimensioned to contain a sufficient volume of a sample, typically about10 to about 50 microliters. In one embodiment of the invention,microtiter plate 624 contains an array 96 of wells 626 arranged in rowsand columns. The number of wells 626 in plate 624 can vary depending onthe manufacturer of the tray, the nature of the samples being analyzedand the process for carrying out the analysis of the sample. Preferably,a bar code 628 is provided on the side wall or the top surface toidentify the respective plate 624 and the samples contained in wells626. Bar code 628 can be used to track the location of the microtiterplate within the apparatus and for cataloging the samples cut from thegel slab.

Referring to FIG. 50, a storage assembly 630 is coupled to cuttingassembly 454 for sequentially supplying a microtiter plate 624 forreceiving gel spots or samples excised from the gel slab. Storageassembly 630 includes a support surface 632 extending from a housing634. Support surface 632 extends through an opening in side wall 596 ofhousing 590 of cutting assembly 454. Support 632 has a top surfacepreferably lying in the same plane as base 594 and is positioned in arecess adjacent the recessed area. In one embodiment, a recess 636 isprovided adjacent support surface 632. Recess 636 includes an inclinedbottom wall that slopes toward an opening to drain any spilled liquidsonto the base. A suitable collection vessel can be placed below theopening to collect the liquids.

Support 632 includes a conveyor 638 extending between housing 634 and anouter end of support 632. In the embodiment illustrated, conveyor 638 isa continuous belt extending from the outer end of support 632 to housing634 as shown in FIG. 50. Conveyor 638 is typically a motor driven belthaving a width that is less than a width of support 632.

The outer end of support 632 defines a work station for receiving amicrotiter plate 624 during the cutting and loading operation of cuttingassembly 454. Storage assembly 630 includes a supply magazine 640 and areceiving magazine 642 coupled to housing 634. Supply magazine 640contains a plurality of stacked microtiter plates which can be dispensedsequentially to conveyor 638.

In operation, a microtiter tray is delivered from supply magazine to theconveyor 638. The conveyor motor is actuated to convey plate 624 to thework station. Robotic arm assembly 592 is then actuated by the computerto excise predetermined samples from the gel and sequentially transferthe excised portion to a respective well 626 of sample microtiter plate624.

After the excised samples from the gel are transferred to samplemicrotiter plate 626, the conveyor is actuated to convey samplemicrotiter plate 624 to a position below receiving magazine 642.Plungers are positioned below receiving magazine 642 to push samplemicrotiter plate 624 upwardly into receiving magazine 642. Detentsretain microtiter plate 624 in receiving magazine 642. One example of asuitable storage assembly that can be used in combination with thecutting assembly is available from Packard Biosciences Corporation andis sold under the tradename Platestack.

At the completion of the cutting process, robotic arm 484 is again movedinto a position to couple to the tray 488 with the gel and gel clamp.Robotic arm 484 is moved to a position immediately below handle of trayso that locking pin 504 is aligned with triangular opening 554. Roboticarm 484 is then raised upwardly so that locking pin 504 passes throughtriangular opening 554. Locking pin 504 is then actuated to move to thelocking position to capture tray 488. Robotic arm 484 slides tray 488outwardly from cutting assembly 454 and returns tray 488 to the inclinedposition shown in FIG. 43. At that time, robotic arm 156 of stainingassembly is aligned with and moved into position to insert the couplingpins 198 through the openings in gel clamp 52. Arms 196 of robotic arm156 are pivoted outwardly to capture the gel clamp. In one embodiment,robotic arm 156 of staining assembly 14 lifts gel clamp 52 upwardly in asubstantially vertical direction to separate gel clamp 52 and gel 36from tray 488. The gel, which is still coupled to the gel clamp 52,slides upwardly along the glass plate until it is lifted completely fromtray 488. In an alternative embodiment, robotic arm 156 moveshorizontally to pull gel clamp 52 and gel 36 away from tray 488 in ahorizontal direction. Tray 488 can be held stationary while robotic arm156 moves away from tray 488. In still another embodiment, tray 488 androbotic arm 156 can be moved apart in a horizontal directionsimultaneously.

After gel clamp 52 and the gel are removed from tray 488, roboticassembly 140 returns the gel and gel clamp 52 to a storage tank of thestaining assembly 14. Preferably, the gel is placed in a liquid, such aswater, so that the gel can be analyzed or processed further at a latertime, if desired. In an alternative embodiment, the gel and the gelclamp 52 are carried to the discarding assembly 402 as shown in FIG. 31where the gel 36 is separated from the clamp 52. The clamp 52 can beremoved from the discard assembly 402 by the robotic assembly 156 andtransferred to a storage rack. Alternatively, the gel clamp 52 can beremoved manually from the discarding assembly 402 and transferred to asuitable storage rack.

The robotic arm 156 of robotic assembly 140 again captures a gel and gelclamp 52 that has been stained and treated according to the selectedprotocol. The gel is transferred to the tray 488 and the scanning andcutting process is repeated. In a preferred embodiment, tray 488 iscleaned before a gel is placed on the tray to remove any broken gelpieces, gel or contaminants remaining on tray 488 that could interferewith the scanning or cutting steps.

Referring to FIGS. 51-54, a cleaning assembly 650 is positioned tocooperate with robotic assembly for manipulating tray 488. As shown inFIG. 51, tray 488 is suspended directly above cleaning assembly 650 withtray 488 oriented in a vertical position. Cleaning assembly 650 includesa tank 652 having a bottom wall 654, side walls 656 and end walls 658.Tank 652 has a dimension to receive tray 488 in its verticalorientation.

A spray assembly 660 is coupled to a top end of each side wall 656 oftank 652. Spray assembly 660 includes mounting legs 662 coupled to therespective side wall 656 for supporting a cross member 664 extendingbetween legs 662. Cross member 664 is oriented above the top end of eachside wall 656 as shown in FIG. 53. A plurality of spray nozzles 666 aremounted on each cross member 664 facing inwardly toward the center oftank 652. Preferably, spray nozzles 666 are spaced apart a distance todirect a spray of wash liquid onto tray 488 to spray and wash both sidesof tray 488 simultaneously. Spray nozzles 666 are connected to a supplyconduit 668 for supplying nozzles with a wash liquid. Supply conduit 668is connected to suitable wash liquid supply source and pump forsupplying a wash liquid under sufficient pressure to remove debris fromtray 488. Preferably, the pump is operatively connected to the centralcomputer to coordinate the spray washing step with the movement of therobotic assembly and tray 488.

The wash liquid can be any suitable liquid that is able to effectivelyclean tray 488 to remove residues and the like from the tray 488. Asuitable wash liquid can be distilled or deionized water. In onepreferred embodiment, the wash liquid contains a volatile liquid orsolvent to enable the wash liquid to evaporate quickly and to wash anyresidual proteins from the tray. In one preferred embodiment, supplyconduit 668 is connected to a water supply through line 669 and supplysource 671 of a second solvent through a line 673. The wash cycle firstdirects a spray 675 of water onto tray 488 for a sufficient time toremove debris or gel fragments. The second solvent is preferablyethanol. After a sufficient wash cycle with water, the ethanol issupplied through line 673 to mix with the water to wash the tray with anethanol/water mixture. The water supply is gradually reduced to increasethe ethanol concentration in the wash liquid until the wash liquidcontains only ethanol with no added water.

Spray assembly 660 also includes an air knife 670 for directing a jet ofdrying air to tray 488. Air knife 670 includes a narrow slot 677 fordirecting a substantially flat air stream 676 onto tray 488. Air knife670 is mounted on cross member 664 and connect to a conduit 672 forsupplying air to nozzles 670. Conduit 672 is connected to a pressuredair source which is controlled by the computer to coordinate the airstream with the manipulation of tray 488. In one embodiment, a suitablefilter is included to remove particulates from the drying air. The airsource typically supplies air at a pressure of about 120 psi to airknife 670. Air knife 670 is a standard air knife that is commerciallyavailable from various manufacturers.

In the method of the invention, the robotic arm supports tray 488vertically above tank 652 as shown in FIG. 51. Tray 488 is then loweredinto tank 652 and spray nozzles 660 are actuated to direct a spray 673of wash liquid onto tray 488. In one embodiment, spray nozzles 660 areactuated while tray is being lowered into tank 652 so that a directspray is applied to the entire surface of the tray. Alternatively, spraynozzles 660 are actuated after the tray 488 is positioned in the tank.Spray nozzles 660 continuously direct spray 675 of the wash liquid ontotray 488 in a generally downward direction with respect to tank 652 fora sufficient time to remove any gel pieces and residue from tray 488.The wash liquid drains downward into tank 652 and exits through a drainopening 674 where the wash liquid is discharged or recycled.

At the end of the cleaning cycle, spray nozzles 660 discontinue the washliquid and air nozzles 670 are actuated. Air nozzles 670 direct an airjet 676 onto tray 488 as shown in FIG. 54. Preferably, air jet 676 isdirected against tray 488 in a generally downward direction withsufficient force to remove excess wash liquid and dry the surfaces oftray 488. In a preferred embodiment, the robotic assembly raises traywhile the air jet 676 is continuously directed to the tray to dry thesurfaces of the tray and blow any remaining droplets of wash liquiddownwardly into tank 652. The air jet 676 is applied for a time and witha force sufficient to dry the tray and remove the wash liquid. Tray 488is then conveyed into position for receiving a gel for scanning andcutting as discussed above.

The electrophoresis gel 36 is very pliable and when wet can stick tomost surfaces. As robotic arm 156 moves toward tray 488, gel 36 sticksto plate 578 of tray 488. More notable, the gels frequently exhibitdimensional changes during the staining process. The different liquidreagents cause the gels to shrink or expand depending on the reagent.While the edge of the gel is clamped in the gel clamp, the clamped edgecannot expand or contact with the rest of the gel which cause the gel todistort. At the end of the gel staining process, the gel in the clamphas a wavy, curtain-like appearance. The distorted gel 36 often capturessmall air bubbles between plate 578 and the gel 36. The bubbles, andparticularly large bubbles, prevent the gel 36 from laying flat on plate578 which can interfere with the scanning of the gel and produceinaccurate or inconsistent results. The scanner in one embodimentilluminates the gel from below with the scanning/imaging detectorpositioned above the gel. The trapped air bubbles can cause theilluminating light to diffract, which results in an incorrect imagebeing scanned and recorded. In one preferred embodiment, the trappedbubbles are substantially removed or at least flattened to enable thegel to lay substantially flat on the plate 578 of tray 488 so that theremaining air bubbles are sufficiently small to minimize or eliminateinterference during scanning and cutting. The air bubbles are removed byapplying a localized downward pressure on the bulges of the gel. Theapplied pressure is sufficient to displace the air bubbles withoutdamaging the gel.

In one embodiment of the invention, a device 710 is provided to removethe air bubbles that are trapped between the gel and tray 488. Referringto FIG. 33, a gel leveling or relaxer device 710 is positioned toreceive a tray 488 containing a gel from robotic arm 484. In a preferredembodiment, gel relaxer device is arranged in a stacked relation withscanner and spot cutter so that robotic arm 484 can insert and removetray 488 from the device.

The gel relaxer device 710 is a stationary device which receives a tray488 and applies a localized pressure on the bulge caused by the trappedair bubbles to displace or expel the air bubble from between the gel andthe plate and to level the gel on the plate. As the tray 488 is insertedinto device 710, the air bubbles are pushed from the bottom end of thegel toward the gel clamp 52 where the air bubbles can escape. After theair bubbles are pushed toward the gel clamp 52, the jaws of the gelclamp 52 are opened to relieve the gripping pressure on the edge of thegel, which then allows the air bubbles to escape, thereby leveling thegel and allowing the gel to lay flat. The jaws are again closed to gripthe gel and then tray 488 is carried to the scanner by robotic arm 484.Typically, the jaws of the gel clamp are opened for about 2-3 seconds.The jaws can be opened and closed a number of times as needed to allowthe gel to lay flat.

Referring to FIGS. 55-65, gel relaxer device 710 includes asubstantially flat base 712 having first end 714 and a second end 716. Apair of parallel guide rails 718 extend between first end 714 and secondend 716 and are spaced apart a distance to receive tray 488. As shown inFIG. 56, guide rails 718 have an inwardly facing slot 720 having adimension to receive the side edges of tray 488. Slot 720 has upper andlower surfaces that diverge outwardly at first end 714 of base 712 todefine inclined portions 722 as shown in FIG. 56. Inclined portions 722are provided at the receiving end of guide rails 718 for guiding tray488 into slots 720.

Preferably, base 712 has a dimension complementing the dimension of tray488 and is able to receive tray 488 with its associated gel and gelclamp. As shown in FIG. 55, a roller 724 having a substantiallycylindrical shape extends between guide rails 718 and is spaced aboveand parallel to base 712. Preferably, roller 724 is orientedsubstantially perpendicular to guide rails 712 and perpendicular to thesliding direction of tray 488 within slots 720 of guide rails 712.

Roller 724 defines a pressing member to contact the bulging portions ofthe gel caused by air bubbles trapped between the gel and plate 578 oftray 488. Roller 724 is mounted on a spindle 726 and is freely rotatablethereon. Spindle 726 includes axial ends 728 having roller bearings 729that are mounted in a U-shaped recess 731 in brackets 730 adjacent eachguide rail 718 to support roller 724 a predetermined distance from base712. Preferably, brackets 730 include a threaded adjusting screw 732extending through a threaded hole in the bottom of brackets 730 toadjust the height of each axial end 728 independently with respect tobase 712. Referring to FIG. 58, U-shaped recess 731 in each bracket 730includes a groove 733 dimensioned to receive a respective bearing 729.Bearings 729 are able to slide freely in a vertical direction within therespective groove 733. As shown in FIG. 58, adjusting screws 732 extendinto the bottom portion of U-shaped groove 733 to support bearings 729at each end of spindle 726 and to adjust the height of roller 724 withrespect to base 712. Preferably, adjusting screws are independentlyadjustable to determine the angle of roller 724 with respect to base712. In preferred embodiments of the invention, adjusting screws 732position roller 724 to be substantially parallel with the plate 578 oftray 488 and the gel supported thereon when tray 488 is inserted intoslots 720 so that roller applies a substantially uniform pressure acrossthe width of the gel.

In one embodiment, bearings 729 are roller bearings having an inner andouter race where spindle 726 is press fitted into the inner race. Theouter race fits within groove 733 and spindle 726 can rotate freely withrespect to the outer race. In this manner, roller 724 can rotate freelyon spindle 726 and spindle 726 can rotate with respect to the outer raceof the bearing and brackets 730. In one embodiment, roller 724 is madefrom a flexible polymeric nylon material that is able to contact the gelwithout tearing or stretching the gel. In other embodiments, the rollercan be made of metal or other materials. In the illustrated embodimentof FIG. 55A, roller 724 is formed in three sections that can rotateindependently on spindle 726.

As shown in FIG. 56, roller 724 is positioned between first end 714 ofbase 712 and second end 716 to cooperate with the gel supported by thetray 488. Preferably, roller 724 is positioned a small distance abovethe gel on tray 488 so that roller 724 does not normally contact the gelwhen the gel is laying flat on plate 574 of tray 488. Referring to FIGS.64 and 65, an air bubble 734 trapped between the gel and plate 574 formsa bulge 736 in the upper surface of the gel. As tray 488 slides alongguide rails 718, roller 724 is spaced above the gel to define a gap 738.Preferably, the size of gap 738 defines the minimum size of bubble 734that can be accepted without air bubble 734 and bulge 736 interferingwith the scanning and cutting of the gel. Preferably, the height ofroller 724 is adjusted to define a gap between roller 724 and gel 36 ofabout 1 mm to about 4 mm, and preferably about 1-2 mm. Typically, thegap is about equal to the thickness of the gel. Tray 488 slides belowroller 724 as shown in FIG. 65 so that bulge 736 contacts the roller724. As tray 488 is moved below the stationary roller 724, the rollerpushes or squeezes air bubble 734 toward the end of the gel where theair bubble can escape from between the gel and the plate 574 of tray488. In preferred embodiments of the invention, the bottom end of tray488 is inserted into slots 720 so that the free edge of the gel slidesbelow roller 724 so that air bubbles 734 are pushed toward the top endwhere the gel is coupled to the gel clamp.

Roller 724 is freely rotatable so that roller 724 is able to rotate withlittle resistance when it makes contact with a bulge to minimize damageto the gel. Bearings 729 ride freely in slot 733 so that the weight ofrollers 724 applies a substantially constant downward force on the gel.In the event roller 724 engages an obstruction in the gel, such as alarge bubble or bulge, the roller is able to slide upward within theslot 731 to prevent the roller from damaging the gel as the gel slidesbeneath the roller. Preferably, roller 724 has a weight to apply apressure on the gel that is sufficient to flatten the bulges withoutdamaging the gel.

Gel relaxer device 710 also includes a gel clamp actuating assembly 740as shown in FIGS. 55 and 56. Assembly 740 includes a clamp actuatingplate member 742 having a substantially planar configuration. Actuatingmember 742 has a first end 744 coupled to a pivot rod 746 and a secondfree end 747. Pivot rod 746 has axial ends 748 pivotally connected tobrackets 750. As shown in FIG. 55, brackets 750 are mounted to base 712adjacent guide rails 718. In the embodiment illustrated, brackets 750are spaced between the first end 714 of base 712 and roller 724.Preferably, brackets 750 are positioned so that when tray 488 is fullyinserted into slots 720 of guide rails 718, the gel clamp supported bytray 488 is positioned below actuating plate member 742. Actuating platemember 742 is assembled to pivot downwardly to engage and open the gelclamp as discussed hereinafter in greater detail. As shown in FIG. 57,plate member 742 is spring biased in the upward disengaging position bya spring 743 having one end coupled to a fixed post and a second endcoupled to rod 746.

Actuating assembly 740 also includes an actuator 752 for operatingactuating plate member 742. Actuator 752 includes a rod 754 positionedabove second free end 747 of actuating plate 742. Rod 754 includes freeends 756 and 758. Free end 756 of rod 754 is pivotally coupled to abracket 750, which is coupled to base 712 adjacent one guide rail 718.Free end 758 of rod 754 is coupled to a motor 762 coupled to base 712adjacent the other guide rail 718. Motor 762 in one embodiment is apneumatic motor that is able to rotate rod 754 about its axis to moveactuating plate member 742. A pump and air control system supplypressurized air through supply lines 763 to operate motor 762 and rotaterod 754 between the disengaged position shown in FIG. 64 and the engagedposition shown in FIG. 65. The air control system for operating the airpump is operatively connected to the computer control system forcoordinating the operation of the actuating assembly with the operationof robotic assembly 484.

Referring to FIG. 55, two parallel arms 764 are coupled to rod 754 andextend radially outward therefrom. Arms 764 have an outer end 766 with aroller cam member 768 coupled to each arm 764. In the illustratedembodiment, cam members 768 are rollers coupled to each arm 764 by a pin770. As shown in FIG. 55, arms 764 are spaced apart a distance to engageactuator plate member 742.

In use, the robotic arm 484 carries a tray 488 with a gel and gel clampto gel relaxer device 710. Tray 488 is inserted into device 710 so thattray 488 and the gel slide below roller 724. As shown in FIGS. 59 and60, as the gel and tray are inserted into device 710, the air bubblestrapped below the gel are pushed toward the gel clamp. Rollers 724 areable to rotate freely as the gel slides below the roller 724. Tray 488is inserted completely into device 710 by the robotic arm as shown inFIGS. 63-65. At that time, motor 762 is actuated to rotate rod 754 andcam members 768 from the horizontal position shown in FIGS. 56 and 63 tothe vertical position shown in FIG. 65. As shown in FIG. 65, cam members768 are pivoted about the axis of rod 754 to engage actuator platemember 742 and pivot actuator plate member 742 about the axis of rod 746downwardly into contact with the movable jaw of the gel clamp to openthe jaws thereby allowing the gel to lay flat on the tray 488. Motor 762is operatively connected to the central operating computer to coordinatethe movement of the motor with the robotic assembly and the location andposition of the tray.

Cam members 768 remain in the engaged position shown in FIG. 65 for apredetermined time to allow the gel to lay substantially flat and toenable the air bubbles below the gel to escape. Generally, the jaws ofthe gel clamp are opened for about 2-4 seconds which has been foundsufficient to allow the air bubbles to escape. In one embodiment, motor768 is actuated to open and close the jaws of the gel clamp two or moretimes to assist in allowing the gel to lay flat. The entire length oftime for the robotic arm to insert tray 488 into gel relaxer 710,flatten the gel, and remove tray 488 is generally about 7-12 seconds. Atthe end of the gel relaxing stage, the cam members 768 are rotatedupwardly so that the gel clamp again clamps onto the edge of the gel.The robotic assembly then removes tray 488 from device 710 and carriesthe tray to the scanner for capturing the image with a known stainpattern and identifies spots to be cut from the gel.

Roller 724 preferably does not contact the surface of the gel except inthe area of the air bubbles and the bulges to minimize stretching ordistortion of the gel as the gel slides below the roller 724. Roller 724is positioned above the normal dimension of the gel to flatten thebulges and expel excess air from the bubble. It is not necessary toeliminate the air bubbles entirely. Preferably, the roller displaces atleast a portion of the air from the bubble and presses the bulges downto enable the gel to lay substantially flat. Contact of the gel with theroller reduces the height and volume of the air bubbles and reduces theheight of the bulges to a suitable dimension that do not interfere withthe scanning and cutting steps. In the illustrated embodiment, theroller is in a fixed location and the gel is moved past the roller toapply a downward pressure onto the bulges so that air bubbles aredisplaced toward the trailing edge of the gel. In other embodiments, thegel is in a fixed location and the roller is moved across the surface ofthe gel. In both arrangements, the localized downward pressure isapplied to the gel to displace air bubbles of a predetermined minimumheight from a first end to a second end of the gel.

The automated apparatus of the invention is controlled and operated by acomputer or central processing unit. FIG. 66 represents the controlsystem for the apparatus, which includes a central processing unitindicated by block 680. The central processing unit 680 is operativelycoupled to loading assembly 12 indicated by block 682, staining assembly14 indicated by block 684, and scanning and cutting assembly indicatedby block 686. The central processing unit 680 receives a signal from thecontrol unit of loading assembly and stores a record of theidentification bar code on the gel clamp and the gel. The centralprocessing unit 680 includes or is connected to a database to identify abiological sample with the gel and gel clamp and selects the appropriatestaining, scanning and cutting protocols for the sample. The centralprocessing unit is operatively connected to drive motor 160 forcontrolling the movement of the robotic assembly along frame 144indicated by block 688, motor 170 for raising and lowering boom 156indicated by block 690, motor 184 for moving the articulated arm alongthe length of boom 156 indicated by block 692 and the actuator device200 for operating the articulated arms 196 indicated by block 694. Thecentral processing unit is also operatively connected to bar code reader215 on robotic assembly 176 indicated by block 196 to identify a gel andgel clamp.

The computer controlled operating system of the invention coordinatesthe various processing steps for treating a plurality of electrophoresisgels. In preferred embodiments of the invention, the computer operatingsystem continuously manipulates a plurality of gels through theapparatus and maintains a record of the location and progress of eachgel as it passes through the respective stages. The operation andmovement of robotic assembly for capturing a gel from a storage tank,transferring the gel to the various treatment tanks and length of timegels remain in the various tanks are controlled and recorded by a maincomputer. The computer is also able to record the identification barcode for a selected gel and monitor the location of the gel throughoutthe processing steps. The computer system also controls the operation ofrobotic assembly 456 indicated by block 698; gel relaxing assembly 710indicated by block 700, scanning device 452 indicated by block 702; andcutting device 454 indicated by block 704.

While various embodiments of the invention have been chosen toillustrate the invention, it will be understood by those skilled in theart that additions and modifications can be made without departing fromthe scope of the invention as defined in the appended claims.

1. An automated apparatus for processing an electrophoresis gelcomprising: a first recording assembly for receiving identifyinginformation of a second dimension electrophoresis gel slab; a secondrecording assembly for receiving identifying information of a gel clampwhere said gel clamp is capable of supporting and transporting said gelslab; and a computer coupled to said first recording assembly and saidsecond recording assembly for cataloging a selected gel slab with aselected gel clamp.
 2. The apparatus of claim 1, wherein said firstrecording assembly comprises a support for receiving a second dimensionelectrophoresis gel cassette having identifying information; and areader for reading said identifying information and sending anidentifying signal to said computer.
 3. The apparatus of claim 2,wherein said identifying information is printed indicia and wherein saidreader is able to read said indicia.
 4. The apparatus of claim 3,wherein said identifying indicia is a bar code and said reader is a barcode reader.
 5. The apparatus of claim 1, wherein said second recordingassembly comprises a support for supporting said gel clamp; and a readerfor reading said identifying information on said gel clamp.
 6. Theapparatus of claim 5, wherein said support receives a plurality of saidgel clamps.
 7. The apparatus of claim 5, wherein said identifyinginformation on said gel clamp is printed indicia and wherein said readeris able to read said printed indicia.
 8. The apparatus of claim 7,wherein said printed information is a bar code and wherein said readeris a bar code reader.
 9. The apparatus of claim 5, wherein-said readeris mounted in a fixed location with respect to said support.
 10. Theapparatus of claim 1, further comprising a manually operated switchcoupled to said first recording assembly and said second recordingassembly.
 11. The apparatus of claim 9, wherein said support comprises arack for receiving a plurality of said gel clamps in a row and whereinsaid reader is oriented to read said identifying information on aselected gel clamp in a predetermined location.
 12. The apparatus ofclaim 11, further comprising a shield to shield said identifyinginformation of said gel clamps from said reader that are not in saidpredetermined location. 13-47. (canceled)
 48. A gel processing apparatusfor processing a second dimension electrophoresis gel slab, saidapparatus comprising: a first gel slab processing device for processingsaid gel slab; a robotic arm assembly for manipulating said gel slab andmaneuvering said gel slab into a substantially horizontal processingposition of said first gel processing device; and an operating computeroperatively coupled to said robotic arm for controlling said robotic armto maneuver said gel slab into said processing position.
 49. Theapparatus of claim 48, wherein said robotic arm is movable between afirst position for receiving said gel slab and said processing position.50. The apparatus of claim 48, wherein said robotic arm includes asubstantially flat support surface for supporting said gel slab.
 51. Theapparatus of claim 49, wherein said first position of said robotic armis at an incline.
 52. The apparatus of claim 48, wherein said roboticarm assembly is movable in a substantially horizontal direction and in asubstantially vertical direction.
 53. The apparatus of claim 52, whereinsaid robotic arm assembly is pivotable about a substantially horizontalaxis between a vertical position and a horizontal position.
 54. Theapparatus of claim 48, further comprising a gel slab supporting memberhaving a dimension for supporting and transporting said gel slab, saidsupporting member being removably coupled to said robotic arm.
 55. Theapparatus of claim 54, wherein said robotic arm assembly includes acoupling assembly for removably coupling to said supporting member. 56.The apparatus of claim 55, wherein said robotic arm assembly is movablebetween a gel receiving position and a horizontal position.
 57. Theapparatus of claim 56, wherein said robotic arm assembly is movable in ahorizontal direction to insert said supporting member and said gel intosaid first processing device.
 58. The apparatus of claim 57, whereinsaid first processing device is a gel scanning device for capturing animage of said gel.
 59. The apparatus of claim 58, wherein said apparatusfurther comprises a second gel slab processing device and wherein saidrobotic assembly is programmed to move said supporting member and saidgel slab from said first processing device to said second processingdevice.
 60. The apparatus of claim 59, wherein said second processingdevice is a cutting device for cutting and excising a gel sample fromsaid gel slab.
 61. The apparatus of claim 54, wherein said gel slab iscoupled to a clamp assembly for griping an edge of said gel slab andsuspending said gel slab in a vertical orientation, and wherein saidsupporting device is dimensioned to receive said clamp.
 62. Theapparatus of claim 48, further comprising a gel relaxing and flatteningdevice for enabling said gel to lay substantially flat on saidsupporting member.
 63. The apparatus of claim 62, wherein said roboticarm assembly is operable to insert said supporting member and gel intosaid relaxing device to flatten said gel.
 64. The apparatus of claim 62,further comprising an actuating device for opening said clamp for a timesufficient to relieve stress in said gel slab and allow said gel slab tolay substantially flat on said support.
 65. The apparatus of claim 64,further comprising a pressing member for applying a localized pressureon said gel to flatten said gel on said supporting member.
 66. Theapparatus of claim 65, wherein said pressing member is a stationaryroller.
 67. The apparatus of claim 66, wherein said relaxing memberincludes a base for supporting said supporting member and wherein saidroller is spaced above said base, said robotic arm assembly beingoperable to insert said supporting member into said relaxing devicewhereby said roller flattens said gel.
 68. The apparatus of claim 48,further comprising a supporting member removably coupled to said roboticassembly for receiving and supporting said gel slab and a washing devicefor washing said support member, and wherein said robotic assembly ismovable to a wash position.
 69. The apparatus of claim 68, wherein saidrobotic arm assembly is operable to move said support member to asubstantially vertical orientation when in said wash position.
 70. Theapparatus of claim 68, wherein said washing device includes a spraynozzle for directing a wash liquid onto said supporting member.
 71. Theapparatus of claim 70, wherein said washing device includes an airoutlet for directing drying air onto said support member.
 72. Theapparatus of claims 68, wherein said washing device comprises aplurality of spray nozzles for spraying a wash liquid to a first sideand to a second side of said supporting member for a time sufficient towash said supporting member, and wherein said robotic arm assembly isoperable to move said supporting member between sides of said supportingmember.
 73. The apparatus of claim 72, wherein said washing deviceincludes an air knife positioned for directing a stream of drying air tosaid first and second sides of said supporting member.
 74. The apparatusof claims 72, further comprising a control system for automaticallyoperating said robotic arm assembly to position said supporting memberin said washing device, operating said spray nozzles to spray washliquid onto said supporting member and to operate said air knife todirect air onto said supporting member.
 75. A method of scanning animage of a stained electrophoresis gel and excising selected gel spotsfrom the gel by an automated assembly, said method comprising the stepsof: capturing said stained electrophoresis gel on a supporting memberthat is removably coupled to an automated arm assembly, transferringsaid supporting member to a gel scanning device by said automatedrobotic arm assembly, scanning said gel and capturing an image of saidgel and identifying selected spots to be excised and generating acutting signal for cutting said selected spots, transferring saidsupporting member from said scanning device to a gel cutting device bysaid automated robotic arm assembly, and directing said cutting signalto said cutting device for automatically operating said cutting deviceand cutting and removing said selected spots from said gel.
 76. A methodof claim 75, further comprising operating said automated arm assembly bya computer control system to transfer said supporting member to saidscanning device.
 77. The method of claim 75, wherein said scanningdevice sends a signal to said control system indicating completion ofsaid scanning step, and said control system actuates said robotic armassembly to transfer said supporting member to said cutting device. 78.The method of claim 77, wherein said cutting device sends a signal tosaid control system indicating completion of said cutting step, and saidcontrol system actuates said robotic arm assembly to remove saidsupporting member from said cutting device.
 79. The method of claim 75,wherein said control system actuates said robotic arm assembly toposition said supporting member in a gel flattening device andflattening said gel on said supporting member.
 80. The method of claim79, further comprising removing air bubbles trapped between saidsupporting member and said gel to flatten said gel.
 81. The method ofclaim 80, wherein said flattening device includes a stationary rollerand said method comprises moving said gel below said roller anddisplacing said air bubbles from between said supporting member and saidgel, said control system actuating said robotic arm assembly to movesaid gel below said roller.
 82. The method of claim 81, furthercomprising transferring said gel and supporting member from said gelflattening device to said scanning device by said robotic arm assembly.83. An apparatus for leveling an electrophoresis gel on a supportingmember, comprising: a base member having a dimension for receiving saidsupporting member and said gel, and a pressing member for applying alocalized pressure toward said base member for leveling said gel on saidsupporting member.
 84. The apparatus of claim 83, wherein said pressingmember is positioned above said base member and substantially parallelthereto.
 85. The apparatus of claim 84, wherein said pressing member isspaced from said base member a distance to contact bulges in said gel.86. The apparatus of claim 85, wherein said pressing member is in afixed location with respect to said base member.
 87. The apparatus ofclaim 86, wherein said pressing member is a cylindrical shaped rollermounted on a shaft, said roller being mounted for free rotation on saidshaft.
 88. The apparatus of claim 86, further comprising a guide memberfor guiding said supporting member below said pressing member.